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Adv Biomed Res 2020,  9:7

Minocycline may be useful to prevent or treat methamphetamine-induced neural cell death: Hypothetic role of autophagia and apoptosis signaling pathway

1 Razi Drug Research Center, Iran University of Medical Sciences, Tehran, Tabriz, Iran
2 Division of Cognitive Neuroscience, University of Tabriz, Tabriz, Iran

Date of Submission12-Oct-2019
Date of Acceptance16-Dec-2019
Date of Web Publication25-Feb-2020

Correspondence Address:
Dr. Majid Motaghinejad
Tehran, Hemmat Highway Beside the Milad Tower, Iran University of Medical Sciences, P.O. Box: 1449614535. Tehran
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/abr.abr_258_19

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How to cite this article:
Sepehr A, Motaghinejad M, Heysieattalab S, Safari S. Minocycline may be useful to prevent or treat methamphetamine-induced neural cell death: Hypothetic role of autophagia and apoptosis signaling pathway. Adv Biomed Res 2020;9:7

How to cite this URL:
Sepehr A, Motaghinejad M, Heysieattalab S, Safari S. Minocycline may be useful to prevent or treat methamphetamine-induced neural cell death: Hypothetic role of autophagia and apoptosis signaling pathway. Adv Biomed Res [serial online] 2020 [cited 2021 Jan 19];9:7. Available from:

Methamphetamine (METH) is a psychostimulant agent, and its neurotoxic and neurobehavioral consequences are serious.[1] Studies indicated that chronic abuse of METH can cause neural cell death in human and animal subjects.[1],[2] Previous studies also showed that chronic abuse of METH can cause neurodegeneration, clear mechanism to these types of neurodegeneration remains unclear, but it seems that neuroinflammatory signaling pathways involved in this manner.[1] By induction of Bcl-2 phosphorylation after beginning an autophagy or apoptosis signal on the cell surface, in particular by activating tumor necrosis factor-alpha (TNF-α) receptor, c-Jun N-terminal kinase (JNK) causes phosphorylation of Bcl-2 which this phenomenon causes inactivation and dissociation of Bcl-2 from Beclin1 or Bax which cause initiation of autophagy or apoptosis respectively and therefore cell death was occurred[3],[4] On the other way, during recent years, using new neuroprotective compounds with therapeutic probability for the treatment of drug abuses induced sequels has been amazingly increased.[5],[6] Minocycline is a broad-spectrum and long-acting antibiotic and possesses anti-inflammatory, neuroprotective, and neural survival properties.[7],[8] Pervious data suggested that minocycline has anti-inflammatory properties and can inhibit TNF-α receptor downstream signaling cascade in the neural cells.[9],[10] Thus, according to the above evidence, we can suggest and have the theory that by inhibition of TNF-receptor activation and downstream JNK/Bcl-2-Beclin1 or Bcl-2/Bax signaling pathways, minocycline will likely inhibit METH-induced apoptosis and autophagia and probably by this mechanism can inhibit METH-induced neurodegeneration and neural cell loss [Figure 1].
Figure 1: Minocycline can inhibit METH-induced TNFR activation and c-Jun N-terminal kinase/Bcl-2-Beclin1 or c-Jun N-terminal kinase/Bcl-2/Bax signaling pathway which may reduce METH-induced autophagia and apoptosis and consequences neurodegeneration. Further, minocycline directly activates mitochondrial biogenesis which leads to inhibition of METH-induced oxidative stress and inflammation. TNFR: TNF-α receptor, METJ: Methamphetamine

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  References Top

Rahimi Borumand M, Motaghinejad M, Motevalian M, Gholami M. Duloxetine by modulating the Akt/GSK3 signaling pathways has neuroprotective effects against methamphetamine-induced neurodegeneration and cognition impairment in rats. Iran J Med Sci 2019; 44:146-54.  Back to cited text no. 1
Casaletto KB, Obermeit L, Morgan EE, Weber E, Franklin DR, Grant I, et al. Depression and executive dysfunction contribute to a metamemory deficit among individuals with methamphetamine use disorders. Addict Behav 2015; 40:45-50.  Back to cited text no. 2
Olmos G, Lladó J. Tumor necrosis factor alpha: A link between neuroinflammation and excitotoxicity. Mediators Inflamm 2014;2014: 861231  Back to cited text no. 3
Poon HF, Abdullah L, Mullan MA, Mullan MJ, Crawford FC. Cocaine-induced oxidative stress precedes cell death in human neuronal progenitor cells. Neurochem Int 2007; 50:69-73.  Back to cited text no. 4
Elkashef A, Vocci F, Hanson G, White J, Wickes W, Tiihonen J. Pharmacotherapy of methamphetamine addiction: An update. Subst Abus 2008; 29:31-49.  Back to cited text no. 5
Ballester J, Valentine G, Sofuoglu M. Pharmacological treatments for methamphetamine addiction: Current status and future directions. Expert Rev Clin Pharmacol 2017; 10:305-14.  Back to cited text no. 6
Miao H, Li R, Han C, Lu X, Zhang H. Minocycline promotes posthemorrhagic neurogenesis via M2 microglia polarization via upregulation of the TrkB/BDNF pathway in rats. J Neurophysiol 2018; 120:1307-17.  Back to cited text no. 7
Scott G, Zetterberg H, Jolly A, Cole JH, De Simoni S, Jenkins PO, et al. Minocycline reduces chronic microglial activation after brain trauma but increases neurodegeneration. Brain 2018; 141:459-71.  Back to cited text no. 8
Stirling DP, Koochesfahani KM, Steeves JD, Tetzlaff W. Minocycline as a neuroprotective agent. Neuroscientist 2005; 11:308-22.  Back to cited text no. 9
Lee SM, Yune TY, Kim SJ, Kim YC, Oh YJ, Markelonis GJ, et al. Minocycline inhibits apoptotic cell death via attenuation of TNF-alpha expression following iNOS/NO induction by lipopolysaccharide in neuron/glia co-cultures. J Neurochem 2004; 91:568-78.  Back to cited text no. 10


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