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Neurotrophic factors and their effects in the treatment of multiple sclerosis
Shahnaz Razavi1, Ghasemi Nazem1, Mohammad Mardani1, Ebrahim Esfandiari1, Hossein Salehi1, Sayyed Hamid Zarkesh Esfahani2
1 Department of Anatomical Sciences and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
2 Department of Biology, Faculty of Sciences, University of Isfahan, Isfahan, Iran
| Date of Submission | 26-Feb-2014 |
| Date of Acceptance | 24-Apr-2014 |
| Date of Web Publication | 17-Feb-2015 |
Correspondence Address:
Shahnaz Razavi
Department of Anatomical Sciences and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan 81744-176
Iran
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/2277-9175.151570
Neurotrophins are small molecules of polypeptides, which include nerve growth factor (NGF) family, glial cell line-derived neurotrophic factor (GDNF) family ligands, and neuropoietic cytokines. These factors have an important role in neural regeneration, remyelination, and regulating the development of the peripheral and central nervous systems (PNS and CNS, respectively) by intracellular signaling through specific receptors. It has been suggested that the pathogenesis of human neurodegenerative disorders may be due to an alteration in the neurotrophic factors and their receptors. The use of neurotrophic factors as therapeutic agents is a novel strategy for restoring and maintaining neuronal function during neurodegenerative disorders such as multiple sclerosis. Innate and adaptive immune responses contribute to pathology of neurodegenerative disorders. Furthermore, autoimmune and mesenchymal stem cells, by the release of neurotrophic factors, have the ability to protect neuronal population and can efficiently suppress the formation of new lesions. So, these cells may be an alternative source for delivering neurotrophic factors into the CNS. Keywords: Glial cell line-derived neurotrophic factor family ligand, multiple sclerosis, neuropoietic cytokines, nerve growth factor family
How to cite this article:
Razavi S, Nazem G, Mardani M, Esfandiari E, Salehi H, Esfahani SH. Neurotrophic factors and their effects in the treatment of multiple sclerosis. Adv Biomed Res 2015;4:53 |
How to cite this URL:
Razavi S, Nazem G, Mardani M, Esfandiari E, Salehi H, Esfahani SH. Neurotrophic factors and their effects in the treatment of multiple sclerosis. Adv Biomed Res [serial online] 2015 [cited 2023 Jun 8];4:53. Available from: https://www.advbiores.net/text.asp?2015/4/1/53/151570 |
| Introduction | |  |
Growth factors are a group of proteins that are able to stimulate the growth of specific tissues and are expressed in a wide range of organisms including humans. [1] These proteins play an important role in regulating various cellular processes including cell proliferation, differentiation, and maturation. Several kinds of growth factors were originally isolated from the tissues of animals. [1] These substances include insulin-like growth factors, epidermal growth factors (EGFs), platelet-derived growth factors, and nerve growth factors (NGFs). Moreover, cytokines are another type of growth factors that are released by a cell to regulate the function of another cell.
Neurotrophic factors include three families of growth factors: NGF family (also known as neurotrophins or NTs), glial cell line-derived neurotrophic factor (GDNF) family ligands, and a heterogeneous group of molecules that belong to the cytokine family. [2] Many studies have shown that neurotrophic factors regulate various cellular processes including calcium homeostasis and blood flow to the brain. Furthermore, they inhibit free radical formation by increasing the levels of antioxidant enzymes. [3],[4] Significant increase in the secretion of NT occurs in specific conditions such as antigen activation, [5] inflammatory infiltration during neurodegenerative diseases, and during demyelinating process. Each of the neurotrophic factors exerts its biological activities through specific Trk family of tyrosine protein kinases [6],[7] and p75 receptor that is a member of the tumor necrosis factor receptor superfamily. [8]
| The ngf family of growth factors | | |
This family of growth factors includes NGF, brain-derived neurotrophic factor (BDNF), NT-3, NT-4 (NT-4/5 or NT-5), [9] and NT-6. [10] In their biologically active form, these growth factors exhibit about 50% amino acid identity. The genes responsible for coding of these NTs are highly expressed not only during the development of nervous system but also in the adult organism. In addition, these genes are highly expressed in a variety of tissues including hippocampus, cerebral cortex, and other parts of central nervous system (CNS). The Trk family of tyrosine protein kinases including TrkA, TrkB, TrkC, and a member of the tumor necrosis factor receptor superfamily (p75) are responsible for the physiological activities of NGF. [11]
Nerve growth factor
NGF is the first member of the NT family to be discovered in 1952 by Levi-Montalcini. [12] High concentrations of NGF were detected in the mouse submandibulary glands. Moreover, under normal conditions, NGF is distributed in high levels in regions of the CNS that are innervated by the magnocellular cholinergic neurons, such as hippocampus, and regions containing the cell bodies of these neurons. [13],[14] The level of NGF in the nervous system and cerebrospinal fluid has been found to decrease with age. [15] NGFs that have a high specific activity on neuronal cells are classified as neurotrophic factors. Structurally, neurotrophic factors are polypeptides and are necessary for the development and maintenance of the vertebrate nervous system, neural regeneration, and remyelination. [2] NGF is essential for the growth, differentiation, regeneration, neurotransmitter function, development, and phenotypic maintenance of neurons in the peripheral nervous system (PNS), and for the functional accuracy of cholinergic neurons in the CNS. [13],[14] The three-dimensional structure of NGF is made up of three subunits, including α, β, and g subunits, which interact to constitute a high-molecular-weight 7S complex that is about 130-140 kDa in weight. [9],[16] The β subunit is responsible for the biological activity of NGF, but the g subunit is an EGF binding protein that has a role in the functions of the β subunit. In addition, the role of the α subunit is not clear. The 2.5S form of NGF has a molecular weight of 26 kDa and is organized by non-covalent interactions of two different subunits. [9],[16]
NGF's biological activity is mediated by a specific receptor, including two receptors, TrkA and p75 neurotrophin receptor (NTR), whose signaling pathways can be synergic, antagonistic, or independent of each other. [17] The p75NTR is a transmembrane glycoprotein that is able to bind to all NTs with different affinities. This receptor has been shown to act as a co-receptor which increases the production of ceramides. Moreover, it activates gene transcription and acts as a mediator in the apoptotic process that is induced by NGF. [17],[18] Trk receptors are composed of three parts including transmembrane, extracellular, and intracellular domains. The cytosolic domain of the Trk receptor is responsible for the tyrosine kinase activity and signal transduction. [17],[19]
TrkA is a 140-kDa transmembrane protein that encoded by proto-oncogenes on chromosome 1. This receptor has a high affinity for NGF. So, the most function of NGF has done by TrkA receptors. After binding of NGF to a TrkA receptor, tyrosine kinase receptor autophosphorylation takes place leading to gene transduction in cells. [17],[19] Some studies show that TrkA receptor has significant effects on the development of the nervous system. Thus, the lack of these receptors can lead to loss of neurons. [17],[19]
NGF has been demonstrated to promote the biosynthesis of myelin component sheaths by myelin forming cells in CNS and PNS, [20],[21] as well as differentiation of oligodendrocytes in experimental autoimmune encephalomyelitis (EAE). [22] In vivo and in vitro studies suggested that because of the beneficial effects of NGF, this factor may be a new good therapeutic tool for the treatment of neurodegenerative diseases. [23],[24]
Brain-derived neurotrophic factor
BDNF is the second member of the NT family that was discovered in 1982 due to its trophic effects in dorsal root ganglion cells [25] and hippocampal and cortical neurons. [26] It is a 27-kDa basic protein and is one of the most potent factors that support neuronal survival, regulating neurotransmitter release and dendritic growth. [27] Traditionally, neurons, [28] activated astrocytes present in inflamed areas of neurodegenerative diseases, [29],[30] and immune cells [30] have been considered the major cellular sources of BDNF. Moreover, the expression of NTs and their respective receptors has also been detected in the lymphoid organs such as thymus and spleen. [31] In line with the above, in vitro studies show that activated T cells, B cells, and monocytes express bioactive BDNF in neurodegenerative lesions. [27],[30] BDNF mRNA and protein levels have a more widespread distribution than NGF since they have been detected in several regions of CNS, such as neocortex, entorhinal cortex, some of the basal ganglia, hippocampus, thalamus, and the superior colliculus. [32] So, BDNF provides trophic support for developing cholinergic, dopaminergic, serotonergic, and gamma-aminobutyric acid (GABA) ergic neurons, and may also have a potential role in promoting the function and survival of other neuronal populations. [33]
BDNF binds with two different types of receptors: TrkB and p75NTR. [34] TrkB receptor exists in two isoforms including gp 145 TrkB or full length receptor and gp 95 TrkB receptor or truncated receptor that lacks the tyrosine kinase domain. [35] BDNF has the ability to act through different mechanisms including trophic mechanisms, neurotransmitter-like axodendritic communication, and by paracrine interactions between neighboring cells. [36] Several studies have shown the therapeutic application of BDNF that it is able to prevent neuronal degeneration after experimental axotomy and other forms of neuronal injury. [37],[38],[39],[40]
NT-3 and NT-4
NT-3 is the third neurotrophic factor that was characterized in 1990 after NGF and BDNF. [41] In humans, this growth factor is encoded by the NT-3 gene and has distinct biological activity. The mature NT-3 has different characteristics from both NGF and BDNF, but displays a structural homology (57-58% amino acid identity) with them. NT-3 was detected in glia and neuronal populations and the level of NT-3 mRNA in the CNS is higher during fetal development than in adult brain. [41] This may indicate that NT-3 has a major role in neuronal survival and differentiation during development. [41],[42] In addition, NT-3 induces profuse neurotic outgrowth from dorsal root ganglion explants, promotes outgrowth from both nodose ganglion and sympathetic ganglion, [43],[44] prevents the death of facial motor neurons, [45] and is essential for the survival of sympathetic and sensory neurons. [46]
The cellular responses to NT-3 are mediated by three receptors that are placed on the surface of cells. [13],[17] TrkC or physiologic receptor is a tyrosine kinase receptor that binds with the greatest affinity to NT-3 and is activated only by NT-3. In contrast to TrkC, TrkB mediates the effects of NT-3 and other neurotrophic factors such as BDNF and neurotrophin-4 (NTF4). Finally, the other NT-3 receptor is a low-affinity nerve growth factor receptor (LNGFR) that plays a somewhat less clear role.
NTF4, also known as neurotrophin-5 (NTF5), was described in 1991. [47] This protein is encoded by the NTF4 gene and signals predominantly through the TrkB and p75NTR receptors. In addition, NTF4 can also interact with TrkA receptor, but with low affinity. A number of recent studies have proposed that NTF4 is able to promote the survival of corticospinal motor neurons in neonatal rats, prevent atrophy of rat rubrospinal neurons after cervical axotomy, and promote axonal regeneration. [48],[49]
| Ngf family of growth factors and multiple sclerosis | | |
Multiple sclerosis (MS) has been explained as a chronic autoimmune demyelinating disease of CNS. Multifocal regions of inflammation into CNS are the primary cause of damage in MS. [50] However, a number of recent studies have proposed that BDNF is the first member of the NGF family that is expressed in areas of inflammation. [2],[27],[30]
Prescription of BDNF protein or BDNF gene can rescue neurons from degeneration and induce axonal outgrowth and regeneration. [51] Many of the identified NT factors such as BDNF can be produced by neurons. These cells are considered to be the major targets for neurotrophic interactions in the CNS. Therefore, neuronal BDNF might also contribute to endogenous neurotrophic support in MS lesions. [52] In the early stages of lesion development, T cells and other immune cells by the release high level of neurotrophic factors have the ability to protect neuronal population (by BDNF and NT3 secretion), enhance neuronal survival (by BDNF, NGF, NT3, and NT4 secretion), promote axon regeneration, and support remyelination (by NGF, GDNF, NT3, and BDNF secretion). [2],[5],[24]
Results of a study on MS patients showed that BDNF production by peripheral blood mononuclear cells is higher during relapse and in the recovery phase, compared to the values detected in the stable phase of the disease. [53] NT factors have a short half-life, and when delivered peripherally, their efficacy is reduced due to the blood-brain barrier. So, autoimmune cells may be an ideal vehicle for delivering neurotrophic factors to the CNS. [54] Studies on patients with MS have shown that endogenous BDNF may play a beneficial role in the pathogenesis of lesion. Moreover, this factor and its receptor were found in the areas of inflammation in the CNS of MS patients. [30] The use of immunosuppressing drugs such as interferon-beta (IFNβ) for MS treatment can stimulate BDNF production. [55] In addition, some studies show that T cells derived from MS patients treated with glatiramer acetate (GA) produce high level of BDNF. [56],[57] In various studies on EAE model of MS was found an increased level of BDNF and its receptor, [58],[59],[60] that activated astrocytes and immune cells which are present in the lesion areas of EAE, are key factors. [27] It was reported that stem cell treatment improved neurological functional recovery in mice model of MS by increasing the production of BDNF. [61],[62],[63] The outcomes of a study with BDNF heterozygous knockout mice proved that BDNF also regulates the number of oligodendrocyte progenitors and myelin protein synthesis. [64] These results support the idea that endogenous BDNF can play a neuroprotective role in the pathogenesis of MS lesion.
| Gdnf family ligands | | |
This family of growth factors consisting of GDNF, neurturin (NTN), persephin (PSPN), and artemin (ARTN) belong to the transforming growth factor (TGF)-β superfamily because they have seven cysteine residues in the same relative spacing. The amino acid sequence homology between the members of the GDNF family ligands (GFLs) is between 40 and 50%, but less than 20% with other members of the TGF-β superfamily. [65] GFLs exert their biological activities by activating the transmembrane RET tyrosine kinase by binding with high affinity to different glycosyl phosphatidylinositol (GPI)-linked GFRα receptors that include GFRα1, GFRα2, GFRα3, and GFRα4. [66] Mammalian GFRα4 is shorter than other GFRα receptors. Binding of ligand-GFRα complex to Ret triggers its homodimerization, phosphorylation, and intracellular signaling, which regulate cell survival, differentiation, proliferation, migration, chemotaxis, branching morphogenesis, neurites outgrowth, and synaptic plasticity. [67]
Glial cell line-derived neurotrophic factor
GDNF was characterized in 1993 as the first member of the GFLs that promotes the survival of many types of neurons such as dopaminergic and motor neurons. [68] In addition, GDNF was able to prevent apoptosis of motor neurons (almost 100 times more efficient survival factor for spinal motor neurons than the NT) as well as regenerate sensory axons after spinal cord injury. [69] GDNF has several functions outside the nervous system. For example, GDNF signaling is an attractive target for the kidney development [65] and spermatogenesis. [70] In humans, this neurotrophic factor is encoded by the GDNF gene. GDNF gene encodes a highly conserved neurotrophic factor that is processed and secreted as a mature protein. Structurally, GDNF is a glycosylated and disulfide bonded homodimer and the molecular weight is approximately 33-45 kDa. [68] GDNF signaling is mediated via a multicomponent receptor complex consisting of two-component receptor: GFRα1 and a transmembrane RET receptor tyrosine. In addition, GDNF crosstalk is weak with other GFRα receptors and can trigger Ret-independent signaling through GFRα1. [71]
Neurturin
NTN is the second member of GFLs that was originally purified and cloned by virtue of its ability to promote the survival of sensorimotor, sympathetic, parasympathetic, and enteric neurons. [72] NTN shares a 40% homology with GDNF. In addition, NTN and GDNF use the same receptors and signaling pathways. Endogenously, NTN binds to a heterotetrameric complex of c-Ket tyrosine kinase receptor and glycosyl phosphatidylinositol-linked proteins, GFRα-2 (GDNFR-α) and GFRα-2, which are high expressed in the adult substantia nigra but not in the adult striatum. [73] In vitro and in vivo studies show that NTN promotes the survival of developing dopaminergic neurons. [74] One hypothesis for this event may be that NTN mRNA is expressed in the ventral midbrain and striatum. [74]
It has been illustrated in a study that immune cells produce NTN and can potentially improve the function and delay the rate of degeneration of neurons in neurodegenerative diseases. [75] Moreover, NTN can stimulate DNA synthesis in spermatogonia. [76]
Artemin
ARTN is the most recent member of GFLs that is able to promote the survival of peripheral ganglia and dopaminergic neurons [77] and regulate the differentiation of autonomic, sensorimotor, and enteric neurons in CNS and PNS. [72]
Similar to other members of GDNF family, such as NTN and PSPN, ARTN is also expressed in the developing kidney, but is less important than GDNF. Moreover, an in vitro study shows that ARTN and PSPN are capable of inducing ureteric branching. [78] ARTN exerts its biological action by a specific receptor including GFRα3. Moreover, it has the ability to crosstalk weakly with other GFRα receptors. [79]
Persephin
PSPN is the fourth member of well-characterized GFLs that could be a good alternative to GDNF and NTN because it lacks affinity to the extracellular matrix and has better pharmacokinetics. [80] Although PSPN is apparently inactive on peripheral neurons, it has prominent neurotrophic activities, in particular for dopaminergic neurons, and can promote the survival and morphological differentiation of basal forebrain cholinergic neurons, motoneurons, and dopaminergic neurons. [81] PSPN is widely expressed in the embryonic and adult brain, [78] but its expression is low in many human tissues including the adrenal gland, newborn spleen, muscles, and testis. [82],[83],[84] An in vitro study has reported that high levels of PSPN increased the number of ureteric buds in kidney explants. [78] Moreover, it could protect the cortical neurons from hypoxia-induced cell death and motor neurons from excitotoxic neuronal death. [85],[86] PSPN exert functions through GFRα4 that is smaller than other GFRα receptors. In addition, the ability of PSPN to interact with any co-receptor other than GFRα4 has never been shown before. [65]
| Gdnf family ligands and ms | | |
GDNF and NTN are the two main members of the GFLs that have been commonly explored for use in the therapy of neurodegenerative diseases.
Studies show that these factors can rescue dopamine neurons in the animal models of Parkinson's disease, as well as motor neurons. [87],[88] Moreover, GDNF can prevent motor neuron degeneration in animal models of amyotrophic lateral sclerosis (ALS), and also, is a highly potent trophic factor for spinal motor neurons [88],[89] and central noradrenergic neurons. [90]
Immune cells and their products are involved in the pathogenesis of MS and are found in the CNS of MS patients. A study demonstrates that different immune cell subsets express the GDNF family ligand and different isoforms of the GFL receptors. [31] So, these data give great hope that GDNF family ligands may be effective as a therapeutic agent in the treatment of several neurodegenerative diseases such as MS.
| Neuropoietic cytokines | | |
Neuropoietic cytokines are small proteins that well known for their role in immune response and play a much greater role in diverse aspects of physiology. This group of growth factors consisting of ciliary neurotrophic factor (CNTF) and leukemia inhibitory factor (LIF) [2] play an important role in the differentiation of astrocytes from neural progenitors and have differential effects on adult neurogenesis. Interestingly, it should be considered that any cell that responds to CNTF could also respond to LIF. [91]
Ciliary neurotrophic factor
CNTF is the first neurotrophic factor that has ability to support the survival of motor neurons and parasympathetic neurons from the chick ciliary ganglion. [92] In addition, CNTF can also promote cholinergic and astrocytic differentiation and enhance the survival of sensorimotor, preganglionic sympathetic, and hippocampal neurons. [93],[94],[95] Unlike the other members of the neuropoietic cytokines such as LIF, high concentrations of CNTF were detected in intact nerves. [96] The cellular responses to CNTF are mediated by a multimeric receptor complex that consists of two elements. [97] The specific binding subunit that anchors to the plasma membrane by gp13o (gp13o is a glycosyl phosphatidylinositol linkage) is found in all neuropoietic cytokine receptors. CNTF receptor complex apparently also includes signaling subunits that consist of LIFR-gp130 heterodimers. [98],[99] The cytoplasmic domains of these molecules are responsible for the intracellular activation of the Janus-activated kinase-signal transducer and activator of transcription (JAK-STAT) and the mitogen-activated protein kinase (MAPK) pathways. [98],[99]
Leukemia inhibitory factor
LIF is well known due to its biological role in augmenting totipotent embryonic stem cell (ESC) self-renewal by activation of the JAK-STAT pathway. [100] LIF has no effect on humans, [101] but is needed for the long-term growth of embryonic human neural stem cells (NSCs). [102],[103] In addition, LIF may promote neurogenesis in the adult human olfactory bulb. [104],[105] So, it has the ability to alter human NSC differentiation. An in vitro study shows that LIF signaling has an important role in promoting astrocyte-like cell formation, [106],[107] myelinization of Schwann-like cells, [108] and stimulating the self-renewal and maintenance of adult NSCs. LIF signaling is mediated by binding to heterodimers of LIF receptor (LIFR) and gp130. [109] As noted above, these heterodimers can also associate with other receptor subunits to bind with other members of neuropoietic cytokines.
Neuropoietic cytokines and MS
Based on the aforementioned findings, CNTF and LIF might represent novel therapeutic agents for neurodegenerative disorders such as MS. [110] Some clinical studies report that an up-regulation of CNTF and LIF occurs in patients with MS, [111],[112] as well as in EAE. [113] A recent report demonstrated that in a CNTF-knockout model of EAE or in the presence of anti-LIF antibodies, there is enhanced oligodendrocyte death that is followed by increased demyelination and a significant increase in the severity of the clinical symptoms. [113] The exact mechanism by which exogenous LIF is able to enhance oligodendrocyte survival and inhibits oligodendrocyte apoptosis is not clear. So, the endogenous protective mechanism versus axonal injury and oligodendrocyte apoptosis depends on the up-regulation of LIF and CNTF in MS. [111],[112] Previous studies suggest that although mutations in LIF and CNTF genes do not seem to be associated with the development of MS, patients with a null mutation in CNTF exhibit increased severity of the disease. [114]
CNTF stimulates myelination [115] process directly with increased proliferation of oligodendrocyte precursors that is signaled by MAP kinase. In addition, CNTF enhances oligodendrocyte precursor survival that is mediated by rapid tyrosine phosphorylation of JAK-STAT. [116] So, recent studies revealed that binding of CNTF to mature oligodendrocytes activates a different combination of JAK and STAT proteins, which enhances the coordinate expression of the subset of myelin-specific genes that are necessary for remyelination. [116] However, cytokines and the ability of these factors in differentiating oligodendrocyte precursor could be of therapeutic value of these factors in the treatment of MS. Salehi et al. showed that CNTF increases myelin oligodendrocyte glycoprotein (MOG) expression and may be important in the pathophysiology of MS. Moreover, CNTF may play a role in the process of remyelination by inducing MOG expression. [117] It is reported that CNTF acts on oligodendrocytes' maturation, and this effect is mediated through the 130-kDa glycoprotein receptor via Janus kinase pathway. [118] Stem cells via CNTF secretion are able reduce demyelination and induce clinical recovery in EAE model of MS through exerting their immunoregulatory activity, inhibiting inflammation, reducing demyelination, and stimulating oligodendrogenesis. [119],[120]
| Conclusion | | |
Here, we explained various neurotrophic factors, their related receptors, and their clinical applications in MS. These factors are small proteins that provide trophic events in neural cells. Moreover, NTFs play an important role in the developing and mature nervous system. Neurotrophic factors act by binding to the specific cell surface receptors that signal the neuron to survive. Stem cells and immune cells are cellular sources of neurotrophic factors. So, these cells, through neurotrophic factor secretion, may have an important role in the treatment of neurodegenerative diseases such as MS.
| Acknowledgment | | |
The authors are grateful to the Iranian Council of Stem Cell Technology, Isfahan University of Medical Sciences for the financial support (Grant no. 189067).
| References | | |
| 1. | Hardy K, Spanos S. Growth factor expression and function in the human and mouse pre implantation embryo. J Endocrinol 2002;2:221-36.  |
| 2. | Kerschensteiner M, Stadelmann C, Dechant G, Wekerle H, Hohlfeld R. Neurotrophic cross-talk between the nervous and immune systems: Implications for neurological diseases. Ann Neurol 2003;53:292-304. |
| 3. | Zhou Z, Chen H, Zhang K, Yang H, Liu J, Huang Q. Protective effect of nerve growth factor on neurons after traumatic brain injury. J Basic Clin Physiol Pharmacol 2003;14:217-24. |
| 4. | Chiaretti A, Antonelli A, Genovese O, Fernandez E, Giuda D, Mariotti P, et al. Intraventricular nerve growth factor infusion improves cerebral blood flow and stimulates double cortin expression in two infants with hypoxic-ischemic brain injury. Neurol Res 2008;30:223-8. |
| 5. | Moalem G, Gdalyahu A, Shani Y, Otten U, Lazarovici P, Cohen IR, et al. Production of neurotrophins by activated T cells: Implications for neuroprotective autoimmunity. J Autoimmun 2000;15:331-45. |
| 6. | Chao MV. Neurotrophin receptors: A window into neuronal differentiation. Neuron 1992;9:583-93. |
| 7. | Barbacid M. The Trk family of neurotrophin receptors. Neurobiol 1994;25:1386-403. |
| 8. | Chao MV. The p75 neurotrophin receptor. Neurobiol 1994;25:1373-385. |
| 9. | Vega JA, Garcia-Suarez O, Hannestad J, Perez- Perez M, Germana A. Neurotrophins and the immune system. J Anat 2003;203:1-19. |
| 10. | Götz R, Köster R, Winkler C, Raulf F, Lottspeich F, Schartl M, et al. Neurotrophin-6 is a new member of the nerve growth factor family. Nature 1994;6503:266-9. |
| 11. | Markus A, Patel TD, Snider WD. Neurotrophic factors and axonal growth. Curr Opin Neurobiol 2002;5:523-31. |
| 12. | Levi-Montalcini R. The nerve growth factor: Thirty-five years later. EMBO J 1987;5:1145-54. |
| 13. | Sofroniew MV, Howe CL, Mobley WC. Nerve growth factors signalling, neuroprotection and neural repair. Annu Rev Neurosci 2001;24:1217-81. |
| 14. | Castellanos MR, Aguiar J, Fernandez CI, Almaguer W, Mejias C, Varela A. Evaluation of the neurorestorative effects of the murine beta-nerve growth factor infusions in old rat with cognitive deficit. Biochem Biophys Res Commun 2003;312:867-72. |
| 15. | Xia YX, Ikeda T, Xia XY, Ikenoue T. Differential neurotrophin levels in cerebrospinal fluid and their changes during development in newborn rat. Neurosci Lett 2000;280:220-2. |
| 16. | Shooter EM. Early days of the nerve growth factor proteins. Annu Rev Neurosci 2001;24:601-29. |
| 17. | Frossard N, Freund V, Advenier C. Nerve growth factor and its receptors in asthma and inflammation. Eur J Pharmacol 2004;500:453-65. |
| 18. | Rankin SL, Guy CS, Mearow KM. TrkA NGF receptor plays a role in the in the modulation of p75NTR expression. Neurosci Lett 2005;383:305-10. |
| 19. | Sofroniew MV, Howe CL, Mobley WC. Nerve growth factors signalling, neuroprotection and neural repair. Annu Rev Neurosci 2001;24:1217-81. |
| 20. | Althaus HH, Kloppner S, Schmidt-Schultz T, Schwartz P. Nerve growth factor induces proliferation and enhances fiber regeneration in oligodendrocytes isolated from adult pig brain. Neurosci Lett 1992;135:219-23. |
| 21. | Urschel BA, Hulsebosch CE. Schwann cell-neuronal interactions in the rat involve nerve growth factor. J Comp Neurol 1990;296:114-22. |
| 22. | Calza L, Giardino L, Pozza M, Micera A, Aloe L. Time-course changes of nerve growth factor, corticotropin-releasing hormone, and nitric oxide synthase isoforms and their possible role in the development of inflammatory response in experimental allergic encephalomyelitis. Proc Natl Acad Sci U S A 1997;94:3368-73. |
| 23. | Salehi A, Delcroix JD, Swaab DF. Alzheimer's disease and NGF signaling. J Neural Transm 2004;111:323-45. |
| 24. | Villoslada P, Hauser SL, Bartke I, Unger J, Heald N, Rosenberg D, et al. Human nerve growth factor protects common marmosets against autoimmune encephalomyelitis by switching the balance of T helper cell type 1 and 2 cytokines within the central nervous system. J Exp Med 2000;191:1799-806. |
| 25. | Barde YA, Edgar D, Thoenen H. Purification of a new neurotrophic factor from mammalian brain. EMBO J 1982;5:549-53. |
| 26. | Huang EJ, Reichardt LF. Neurotrophins: Roles in neuronal development and function. Annu Rev Neurosci 2001;24:677-736. |
| 27. | Kerschensteiner M, Gallmeier E, Behrens L. Activated human Tcells, B cells, and monocytes produce brain-derived neurotrophic factor in vitro and in inflammatory brain lesions: A neuroprotective role of inflammation. J Exp Med 1999;189:865-70. |
| 28. | Lewin GR, Barde YA. Physiology of the neurotrophins. Annu Rev Neurosci 1996;19:289-317. |
| 29. | Burbach GJ, Hellweg R, Haas CA, Del TD, Deicke U, Abramowski D, et al. Induction of brain-derived neurotrophic factor in plaque-associated glial cells of aged APP23 transgenic mice. J Neurosci 2004;24:2421-30. |
| 30. | Stadelmann C, Kerschensteiner M, Misgeld T, Bruck W, Hohlfeld R, Lassmann H. BDNF and gp145trkB in multiple sclerosis brain lesions: Neuroprotective interactions between immune and neuronal cells. Brain 2002;125:75-85. |
| 31. | Vargas-Leal V, Bruno R, Derfuss T, Krumbholz M, Hohlfeld R, Meinl E. Expression and function of glial cell line-derived neurotrophic factor family ligands and their receptors on human immune cells. J Immunol 2005;4:2301-8. |
| 32. | Dragunow M, Faull RL, Lawlor P, Beilharz EJ, Singleton K, Walker EB, et al. In situ evidence for DNA fragmentation in Huntington's disease striatum and Alzheimer's disease temporal lobes. Neuro Report 1995;6:61053-7. |
| 33. | Studer L, Spenger C, Seiler RW, Othberg A, Lindvall O, Odin P. Effect of brain-derived neurotrophic factor on neuronal structure of dopaminergic neurons in dissociated cultures of human fetal mesencephalon. Exp Brain Res 1996;108:328-36. |
| 34. | Bothwell M. Functional interactions of neurotrophins and neurotrophin receptors. Annu Rev Neurosci 1995;18:223-53. |
| 35. | Klein R, Conway D, Parada LF, Barbacid MC. The trkB tyrosine protein kinase gene codes for a second neurogenic receptor that lacks the catalytic kinase domain. Cell 1990 18;61:647-56. |
| 36. | Angelucci F, Brenè S, Mathé AA. BDNF in schizophrenia, depression and corresponding animal models. Mol Psychiatry 2005;4:345-52. |
| 37. | Gravel C, Götz R, Lorrain A, Sendtner M. Adenoviral gene transfer of ciliary neurotrophic factor and brain-derived neurotrophic factor leads to long-term survival of axotomized motor neurons. Nat Med 1997;3:765-70. |
| 38. | Kobayashi NR, Fan DP, GiehlK M, Bedard AM, Wiegand SJ, Tetzlaff W. BDNF and NT-4/5prevent atrophy of rat rubrospinal neurons after cervical axotomy, stimulate GAP-43 and Ta1-tubulin mRNA expression, and promote axonal regeneration. J Neurosci 1997;17:9583-95. |
| 39. | Mc Tigue DM, Horner PJ, Stokes BT, Gage FH. Neurotrophin-3 and brain-derived neurotrophic factor induce oligodendrocyte proliferation and myelination of regenerating axons in the contused adult rat spinal cord. J Neurosci 1998;18:5354-65. |
| 40. | Yan Q, Elliott J, Snider WD. Brain-derived neurotrophic factor rescues spinal motor neurons from axotomy-induced cell death. Nature 1992;360:753-5. |
| 41. | Maisonpierre PC, Belluscio L, Squinto S, Ip NY, Furth ME, Lindsay RM, et al. Neurotrophin-3: A neurotrophic factor related to NGF and BDNF. Science 1990;247:1146-451. |
| 42. | Ernfors P, Ibanez CF, Ebendal T, Olson L, Persson H. Molecular cloning and neurotrophic activities of a protein with structural imilarities to nerve growth factor: Developmental and topographical expression in the brain. Proc Natl Acad Sci 1990;87:5454-8. |
| 43. | Holtzman DM, Mobley WC. Neurotrophic factors and neurologic disease. West J Med 1994;161:246-54. |
| 44. | Thoenen H. The changing scene of neurotrophic factors. Trends Neurosci 1991;14:165-70. |
| 45. | Arenas E, Persson H. Neurotrophin-3 prevents the death of adult central noradrenergic neurons in vivo. Nature 1994;367:368-71. |
| 46. | Farinas I, Jones KR, Backus C, Wang XY, Reichardt LF. Severe sensory and sympathetic deficits in mice lacking neurotrophin-3. Nature 1994;369:658-61. |
| 47. | Hallbook F, Ibanez CF, Persson H. Evolutionary studies of the nerve growth factor family reveal a novel member abundantly expressed in Xenopus ovary. Neuron 1991;6:845-58. |
| 48. | Kobayashi NR, Fan DP, Giehl KM, Bedard AM, Wiegand SJ, Tetzlaff W. BDNF and NT-4/5prevent atrophy of rat rubrospinal neurons after cervical axotomy, stimulate GAP-43 and Ta1-tubulin mRNA expression, and promote axonal regeneration. J Neurosci 1997;17:9583-95. |
| 49. | Junger H, Varon S. Neurotrophin-4 (NT-4) and glial cell line-derived neurotrophic factor (GDNF) promote the survival of corticospinal motorneurons of neonatal rats in vitro. Brain Res 1997;762:56-60. |
| 50. | Loma I, Heyman R. Multiple sclerosis: Pathogenesis and treatment. Curr Neuropharmacol 2011;3:409-16. |
| 51. | Sendtner M, Holtmann B, Kolbeck R, Thoenen H, Barde YA. Brain-derived neurotrophic factor prevents the death of motoneurons in newborn rats after nervesection. Nature 1992;360:757-9. |
| 52. | Linker RA, Lee DH, Demir S, Wiese S, Kruse N, Siglienti I, et al. Functional role of brain-derived neurotrophic factor in neuroprotective autoimmunity: Therapeutic implications in a model of multiple sclerosis. Brain 2010;8:2248-63. |
| 53. | Sarchielli P, Greco L, Stipa A, Floridi A, Gallai V. Brain-derived neurotrophic factor in patients with multiple sclerosis. J Neuroimmunol 2002;132:180-8. |
| 54. | Kramer R, Zhang Y, Gehrmann J, Gold R, Thoenen H, Wekerle H. Gene transfer through the blood nerve barrier: Nerve growth factor engineered neuritogenic T lymphocytes attenuate experimental autoimmune neuritis. Nat Med 1995;1:1162-6. |
| 55. | Caggiula M, Batocchi AP, Frisullo G, Angelucci F, Patanella AK, Sancricca C, et al. Neurotrophic factors in relapsing remitting and secondary progressive multiple sclerosis patients during interferon beta therapy. Clin Immunol 2006;118:77-82. |
| 56. | Chen M, Valenzuela RM, Dhib-Jalbut S. Glatiramer acetate reactive T-cells produce brain derived neurotrophic factor (BDNF). J Neurol Sci 2003;140:37-44. |
| 57. | Azoulay D, Vachapova V, Shihman B, Miler A, Karni A. Lower brain-derived neurotrophic factor in serum of relapsing remitting MS: Reversal by glatiramer acetate. J Neuroimmunol 2005;167:215-8. |
| 58. | Aharoni R, Eilam R, Domev H, Labunskay G, Sela M, Arnon R. The immunomodulator glatiramer acetate augments the expression of neurotrophic factors in brains of experimental autoimmune encephalomyelitis mice. Proc Natl Acad Sci U S A 2005;102:19045-50. |
| 59. | De Santi L, Annunziata P, Sessa E, Bramanti P. Brainderived neurotrophic factor and TrkB receptor in experimental autoimmune encephalomyelitis and multiple sclerosis. J Neurol Sci 2009;287:17-26. |
| 60. | Colombo E, Cordiglieri C, Melli G, Newcombe J, Krumbholz M, Parada LF, et al. Stimulation of the neurotrophin receptor TrkB on astrocytes drives nitric oxide production and neurodegeneration. J Exp Med 2012;209:521-35. |
| 61. | Zhang J, Li Y, Chen J, Cui Y, Lu M, Elias SB, et al. Human bone marrow stromal cell treatment improves neurological functional recovery in EAE mice. Exp Neurol 2005;195:16-26. |
| 62. | Ghasemi N, Razavi S, Mardani M, Esfandiari E, Salehi H, Zarkesh Esfahani SH. Transplantation of human adipose-derived stem cells enhances remyelination in lysolecithin-induced focal demyelination of rat spinal cord. Mol Biotechnol. 2014; 56:470-8. |
| 63. | Constantin G, Marconi S, Rossi B, Angiari S, Calderan L, Anghileri E, et al. Adipose-derived mesenchymal stem cells ameliorate chronic experimental autoimmune encephalomyelitis. Stem Cells 2009;27:2624-35. |
| 64. | VonDran MW, Singh H, Honeywell JZ, Dreyfus CF. Levels of BDNF impact oligodendrocyte lineage cells following a cuprizone lesion. J Neurosci 2011;31:14182-90. |
| 65. | Eigenbrot C, Gerber N. X-ray structure of glial cell derived neurotrophic factor at 1.9 AÊ resolution and implications for receptor binding. Nat Struct Biol 1997;4:435-8. |
| 66. | Airaksinen MS, Saarma M. The GDNF family: Signalling, biological functions and therapeutic value. Nat Rev Neurosci 2002;3:383-94. |
| 67. | Jing S, Wen D, Yu Y, Holst PL, Luo Y, Fang M, et al. GDNF-induced activation of the ret protein tyrosine kinase is mediated by GDNFR-alpha, a novel receptor for GDNF. Cell 1996;85:1113-24. |
| 68. | Lin LF, Doherty DH, Lile JD, Bektesh S, Collins F. GDNF: A glial cell line-derived neurotrophic factor for midbrain dopaminergic neurones. Science 1993;260:1130-2. |
| 69. | Ramer MS, Priestley JV, McMahon SB. Functional regeneration of sensory axons into the adult spinal cord. Nature 2000;6767:312-6. |
| 70. | Meng X, de Rooij DG, Westerdahl K, Saarma M, Sariola H. Promotion of seminomatous tumors by targeted over expression of glial cell line-derived neurotrophic factor in mouse testis. Cancer Res 2001;61:3267-71. |
| 71. | Treanor JJ, Goodman L, de Sauvage F, Stone DM, Poulsen KT, Beck CD, et al. Characterization of a multicomponent receptor for GDNF. Nature 1996;382:80-3. |
| 72. | Heuckeroth RO, Enomoto H, Grider JR, Golden JP, Hanke JA, Jackman A, et al. Gene targeting reveals a critical role forneurturin in the development and maintenance of enteric, sensory and parasympathetic neurons. Neuron 1999;22:253-63. |
| 73. | Burazin TC, Gundlach AL. Localizationof GDNF/neurturin receptor (c ret, GFRalpha-1and alpha-2) mRNAs in post natal rat brain: Differential regional and temporal expression in hippocampus, cortex and cerebellum. Mol Brain Res 1999;73:151-71. |
| 74. | Horger BA, Nishimura MC, Armanini MP, Wang LC, Poulsen KT, Rosenblad C, et al. Neurturin exertspotentactionsonsur vivalandfunction of midbraindopami - nergicneurons. J Neurosci 1998;18:4929-37. |
| 75. | Gasmi M, Herzog CD, Brandon EP, Cunningham JJ, Ramirez GA, Ketchum ET, et al. Striatal delivery of neurturin by CERE-120, an AAV2 vector for the treatment of dopaminergic neurondegeneration in Parkinson's disease. Mol Ther 2007;15:62-8. |
| 76. | Viglietto G, Dolci S, Bruni P, Baldassarre G, Chiariotti L, Melillo RM, et al. Glial cell line-derived neutrotrophic factor and neurturin can act as paracrine growth factors stimulating DNA synthesis of RET-expressing spermatogonia. Int J Oncol 2000;16:689-94. |
| 77. | Baloh RH, Tansey MG, Lampe PA, Fahrner TJ, Enomoto H, Simburger KS, et al. Artemin, a novel member of the GDNF ligand family, supports peripheral and central neurons and signals through the GFRa3-RET receptor complex. Neuron 1998;21:1291-302. |
| 78. | Milbrandt J, De Sauvage FJ, Fahrner TJ, Baloh RH, Leitner ML, Tansey MG, et al. Persephin, a novel neurotrophic factor related to GDNF and neurturin. Neuron 1998;20:245-53. |
| 79. | Airaksinen MS, Titievsky A, Saarma M. GDNF family neurotrophic factor signalling: Four masters one servant? Mol Cell Neurosci 1999;13:313-25. |
| 80. | Bespalov MM, Sidorova YA, Tumova S, Ahonen-Bishopp A, Magalhães AC, Kulesskiy E, et al. Heparan sulfate proteoglycan syndecan-3 is a novel receptor for GDNF, neurturin, and artemin. J Cell Biol 2011;10:153-69. |
| 81. | Zihlmann KB, Ducray AD, Schaller B, Huber AW, Krebs SH, Andres RH, et al. The GDNF family members neurturin, artemin and persephin promote the morphological differentiation of cultured ventral mesencephalic dopaminergic neurons. Brain Res Bull 2005;68:42-53. |
| 82. | Lindahl M, Timmusk T, Rossi J, Saarma M, Airaksinen MS. Expression and alternative splicing of mouse Gfra4 suggest roles in endocrine cell development. Mol Cell Neurosci 2000;15:522-33. |
| 83. | Lindahl M, Poteryaev D, Yu L, Arumäe U, Timmusk T, Bongarzone I, et al. Human glial cell line-derivedneurotrophic factor receptor alpha 4 is the receptor for persephin and is predominantly expressed in normal and malignant thyroid medullary cells. J Biol Chem 2001;276:9344-51. |
| 84. | Lindfors PH, Lindahl M, Rossi J, Saarma M, Airaksinen MS. Ablation of persephin receptor glial cell line-derived neurotrophic factor family receptoralpha4 impairs thyroid calcitonin production in young mice. Endocrinology 2006;147:2237-44. |
| 85. | Ho TW, Bristol LA, Coccia C, Li Y, Milbrandt J, Johnson E, et al. TGF beta trophic factors differentially modulate motor axon outgrowth and protection from excitotoxicity. Exp Neurol 2000;161:664-75. |
| 86. | Tomac AC, Agulnick AD, Haughey N, Chang CF, Zhang Y, Bäckman C, et al. Effects of cerebral ischemia in mice deficient in persephin. Proc Natl Acad Sci 2002;99:9521-6. |
| 87. | Bilang-Bleuel A, Revah F, Colin P, Locquet I, Robert JJ, Mallet J, et al. Intra striatal injection of an adenoviral vector expressing glial-cell-line derived neurotrophic factor prevents dopaminergic neuron degeneration and behavioral impairment in a rat model of Parkinson disease. Proc Natl Acad Sci U S A 1997;94:8818-23. |
| 88. | Gash DM, Zhang Z, Ai Y, Grondin R, Coffey R, Gerhardt GA. Trophic factor distribution predicts functional recovery in parkinsonian monkeys. Ann Neurol 2005;58:224-33. |
| 89. | Henderson CE, Phillips HS, Pollock RA, Davies AM, Lemeulle C, Armanini M, et al. GDNF: A potent survival factor for motoneurons present in peripheral nerve and muscle. Science 1994;266:1062-4. |
| 90. | Arenas E, Trupp M, Åkerud P, Ibañéz CF. GDNF prevents degeneration and promotes the phenotype of brain noradrenergic neurons in vivo. Neuron 1995;15:1465-73. |
| 91. | Bauer S, Patterson PH. Leukemia inhibitory factor promotes neural stem cell self-renewal in the adult brain. J Neurosci 2006;26:12089-99. |
| 92. | Lin LF, Mismer D, Lile JD, Armes LG, Butler ET, Vannice JL, et al. Purification, cloning and expression of ciliary neurotrophic factor (CNTF). Science 1989;246:1023-5. |
| 93. | Ernsberger U, Sendtner M, Rohrer H. Proliferation and differentiation of embryonic chick sympathetic neurons: Effects of ciliary neurotrophic factor. Neuron 1989;2:1275-84. |
| 94. | Saadat S, Sendtner M, Rohrer H. Ciliary neurotrophic factor induces cholinergic differentiation of rat sympathetic neurons in culture. J Cell Biol 1989;708:1807-16. |
| 95. | Lillien LE, Sendtner M, Rohrer H, Hughes SM, Raff MC. Type-2 astrocyte development in rat brain cultures is initiated by a CNTF-like protein produced by type-l astrocytes. Neuron 1988;1:485-94. |
| 96. | Stockli KA . Molecular cloning, expression and regional distribution of rat ciliary neurotrophic factor. Nature 1989;342:920-3. |
| 97. | Shimazaki T, Shingo T, Weiss S. The ciliary neurotrophic factor/leukemia inhibitory factor/gp130 receptor complex operates in the maintenance of mammalian forebrain neural stem cells. J Neurosci 2001;21:7642-53. |
| 98. | Stahl N, Yancopoulos CD. The alphas, betas, and kinases of cytokine receptor complexes. Cell 1993;74:587-90. |
| 99. | Davis S, Yancopoulos GD. The molecular biology of the CNTF receptor. Curr Opin Cell Biol 1993;2:281-5. |
| 100. | Williams RL . Myeloid leukaemia inhibitory factor maintains the developmental potential of embryonic stem cells. Nature 1988;336:684-7. |
| 101. | Thomson JA . Embryonic stem cell lines derived from human blastocysts. Science 1998;282:1145-7. |
| 102. | Carpenter MK. In vitro expansion of a multipotent population of human neural progenitor cells. Exp Neurol 1999;158:265-78. |
| 103. | Wright LS. Gene expression in human neural stem cells: Effects of leukemia inhibitory factor. J Neurochem 2003;86:179-95. |
| 104. | Galli R, Pagano SF, Gritti A, Vescovi AL. Regulation of neuronal differentiation in human CNS stem cell progeny by leukemia inhibitory factor. Dev Neurosci 2000;22:86-95. |
| 105. | Pagano SF, Impagnatiello F, Girelli M, Cova L, Grioni E, Onofri M, et al. Isolation and characterization of neural stem cells from the adult human olfactory bulb. Stem Cells 2000;18:295-300. |
| 106. | Bonaguidi MA, McGuire T, Hu M, Kan L, Samanta J, Kessler JA. LIF and BMP signaling generate separate and discrete types of GFAP expressing cells. Development 2005;132:5503-14. |
| 107. | Pitman M, Emery B, Binder M, Wang S, Butzkueven H, Kilpatrick TJ. LIF receptor signaling modulates neural stem cell renewal. Mol Cell Neurosci 2004;27:255-66. |
| 108. | Razavi S, Mardani M, Kazemi M, Esfandiari E, Narimani M, Esmaeili A, et al. Effect of leukemia inhibitory factor on the myelinogenic ability of Schwann-like cells induced from human adipose-derived stem cells. Cell Mol Neurobiol 2013;2:283-90. |
| 109. | Gearing DP, Thut CJ, VandenBos T, Gimpel SD, Delaney PB, King J, et al. Leukemia inhibitory factor receptor is structurally related to the IL-6 signal transducer, gpl30. EMBO J 1991;70:2839-48. |
| 110. | Marmur R, Kessler JA, Zhu G, Gokhan S, Mehler MF. Differentiation of oligodendroglial progenitors derived from cortical multipotent cells requires extrinsic signals including activation of gp130/LIF_ receptors. J Neurosci 1998;18:9800-11. |
| 111. | Schonrock LM, Gawlowski G, Bruck W. Interleukin-6 expression in human multiple sclerosis lesions. Neurosci Lett 2000;294:45-8. |
| 112. | Vanderlocht J, Hellings N, Hendriks JJ, Vandenabeele F, Moreels M, Buntinx M, et al. Leukemia inhibitory factor is produced by myelin-reactive T cells from multiple sclerosis patients and protects against tumor necrosis factor-α-induced oligodendrocyte apoptosis. J Neurosci Res 2006;83:763-74. |
| 113. | Butzkueven H, Emery B, Ciprian T, Marriott MP, Kilpatrick TJ. Endogenous leukemia inhibitory factor production limits autoimmune demyelination and oligodendrocyte loss. Glia 2006;53:696-703. |
| 114. | Giess R, Mäurer M, Linker R, Gold R, Warmuth-Metz M, Toyka KV, et al. Association of a null mutation in the CNTF gene with early onset of multiple sclerosis. Arch Neurol 2002;59:407-9. |
| 115. | Ishibashi T, Dakin KA, Stevens B, Lee PR, Kozlov SV, Stewart CL, et al. Astrocytes promote myelination in response to electrical impulses. Neuron 2006;49:823-32. |
| 116. | Dell'Albani P, Kahn MA, Cole R, Condorelli DF, Giuffrida-Stella AM, deVellis J. Oligodendroglial survival factors, PDGF-AA and CNTF, activate similar JAK/STAT signaling pathways. J Neurosci Res 1998;54:191-205. |
| 117. | Salehi Z, Hadiyan SP, Navidi R. Ciliary neurotrophic factor role in myelin oligodendrocyte glycoprotein expression in Cuprizone-induced multiple sclerosis mice. Cell Mol Neurobiol 2013;33:531-5. |
| 118. | Stankoff B, Aigrot MS, Noël F, Wattilliaux A, Zalc B, Lubetzki C. Ciliary neurotrophic factor (CNTF) enhances myelin formation: A novel role for CNTF and CNTF-related molecules. J Neurosci 2002;2:9221-7. |
| 119. | Lu Z, Hu X, Zhu C, Wang D, Zheng X, Liu Q. Overexpression of CNTF in Mesenchymal Stem Cells reduces demyelination and induces clinical recovery in experimental autoimmune encephalomyelitis mice. J Neuroimmunol 2009;206:58-69. |
| 120. | Razavi S, Razavi MR, Zarkesh Esfahani H, Kazemi M, Mostafavi FS. Comparing brain-derived neurotrophic factor and ciliary neurotrophic factor secretion of induced neurotrophic factor secreting cells from human adipose and bone marrow-derived stem cells. Dev Growth Differ 2013;55:648-55. |
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| Qi Zheng,Lei Liu,Haolong Liu,Hong Zheng,Hao Sun,Jing Ji,Yaqin Sun,Tao Yang,Hui Zhao,Fang Qi,Kangning Li,Junling Li,Nan Zhang,Yongping Fan,Lei Wang | | Frontiers in Pharmacology. 2019; 10 | | [Pubmed] | [DOI] | | | 30 |
Neuroregeneration in Parkinson’s Disease: From Proteins to Small Molecules |
|
| Yulia A. Sidorova,Konstantin P. Volcho,Nariman F. Salakhutdinov | | Current Neuropharmacology. 2019; 17(3): 268 | | [Pubmed] | [DOI] | | | 31 |
3D Synthetic Peptide-based Architectures for the Engineering of the Enteric Nervous System |
|
| Paola Brun,Annj Zamuner,Alessandro Peretti,Jessica Conti,Grazia M. L. Messina,Giovanni Marletta,Monica Dettin | | Scientific Reports. 2019; 9(1) | | [Pubmed] | [DOI] | | | 32 |
Investigation of Neuregulin-1 and Glial Cell-Derived Neurotrophic Factor in Rodent Astrocytes and Microglia |
|
| Jessica Kronenberg,Lukas Merkel,Sandra Heckers,Viktoria Gudi,H. Markus Schwab,Martin Stangel | | Journal of Molecular Neuroscience. 2019; | | [Pubmed] | [DOI] | | | 33 |
Miro1 Enhances Mitochondria Transfer from Multipotent Mesenchymal Stem Cells (MMSC) to Neural Cells and Improves the Efficacy of Cell Recovery |
|
| Valentina Babenko,Denis Silachev,Vasily Popkov,Ljubava Zorova,Irina Pevzner,Egor Plotnikov,Gennady Sukhikh,Dmitry Zorov | | Molecules. 2018; 23(3): 687 | | [Pubmed] | [DOI] | | | 34 |
Circulating levels of neurotrophic factors are unchanged in patients with Parkinsonæs disease |
|
| Natalia Pessoa Rocha,João Paulo Sampaio Ferreira,Paula Luciana Scalzo,Izabela Guimarães Barbosa,Mariana Soares de Souza,Paulo Pereira Christo,Helton José Reis,Antonio Lucio Teixeira | | Arquivos de Neuro-Psiquiatria. 2018; 76(5): 310 | | [Pubmed] | [DOI] | | | 35 |
FSD-C10, a Fasudil derivative, promotes neuroregeneration through indirect and direct mechanisms |
|
| Yan-Hua Li,Chong Xie,Yuan Zhang,Xing Li,Hai-fei Zhang,Qing Wang,Zhi Chai,Bao-guo Xiao,Rodolfo Thome,Guang-Xian Zhang,Cun-gen Ma | | Scientific Reports. 2017; 7: 41227 | | [Pubmed] | [DOI] | | | 36 |
Brain-derived neurotrophic factor levels under chronic natalizumab treatment in multiple sclerosis. A preliminary report |
|
| Vitalie Vacaras,Zoltán Zsigmond Major,Anca Dana Buzoianu | | Neurologia i Neurochirurgia Polska. 2017; 51(3): 221 | | [Pubmed] | [DOI] | | | 37 |
Functional dissection of astrocyte-secreted proteins: Implications in brain health and diseases |
|
| Mithilesh Kumar Jha,Jong-Heon Kim,Gyun Jee Song,Won-Ha Lee,In-Kyu Lee,Ho-Won Lee,Seong Soo A. An,SangYun Kim,Kyoungho Suk | | Progress in Neurobiology. 2017; | | [Pubmed] | [DOI] | | | 38 |
Rapid Serum-Free Isolation of Oligodendrocyte Progenitor Cells from Adult Rat Spinal Cord |
|
| John Bianco,Dario Carradori,Ronald Deumens,Anne des Rieux | | Stem Cell Reviews and Reports. 2017; 13(4): 499 | | [Pubmed] | [DOI] | | | 39 |
rHIgM22 enhances remyelination in the brain of the cuprizone mouse model of demyelination |
|
| Ariana P. Mullin,Charlene Cui,Yu Wang,Jing Wang,Erika Troy,Anthony O. Caggiano,Tom J. Parry,Raymond W. Colburn,Elias Pavlopoulos | | Neurobiology of Disease. 2017; 105: 142 | | [Pubmed] | [DOI] | | | 40 |
Neurons of the rat cervical spinal cord express vimentin and neurofilament after intraparenchymal injection of kainic acid |
|
| Fabián Nishida,María S. Sisti,Carolina N. Zanuzzi,Claudio G. Barbeito,Enrique L. Portiansky | | Neuroscience Letters. 2017; 643: 103 | | [Pubmed] | [DOI] | | | 41 |
IL-6 Contributes to Corneal Nerve Degeneration after Herpes Simplex Virus Type I Infection |
|
| Ana J. Chucair-Elliott,Jeremy Jinkins,Meghan M. Carr,Daniel J.J. Carr | | The American Journal of Pathology. 2016; | | [Pubmed] | [DOI] | | | 42 |
Intranasal Delivery of Umbilical Cord-Derived Mesenchymal Stem Cells Preserves Myelination in Perinatal Brain Damage |
|
| Byron Oppliger,Marianne Joerger-Messerli,Martin Mueller,Ursula Reinhart,Philipp Schneider,Daniel V. Surbek,Andreina Schoeberlein | | Stem Cells and Development. 2016; 25(16): 1234 | | [Pubmed] | [DOI] | | | 43 |
Potential therapeutic action of natural products from traditional Chinese medicine on Alzheimeræs disease animal models targeting neurotrophic factors |
|
| Shuyong Wei | | Fundamental & Clinical Pharmacology. 2016; | | [Pubmed] | [DOI] | |
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