Methamphetamine induced neurotoxic diseases, molecular mechanism, and current treatment strategies

• Published in: Biomedicine & pharmacotherapy Vol. 154; p. 113591
• Main Authors: Shrestha, Prabhat, Katila, Nikita, Lee, Sooyeun, Seo, Ji Hae, Jeong, Jee-Heon, Yook, Simmyung
• Format: Journal Article
• Language: English
• Published: Elsevier Masson SAS 01.10.2022; Elsevier
• Subjects: Excitotoxicity; Methamphetamine; Neurotoxic disease; Neurotoxicity; Oxidative stress; Targeted therapy; ATF2; Oxidative stress; AMPA; BBB; ROCK2; Targeted therapy; KLH; PARP; Neurotoxic disease; MDMA; Neurotoxicity; VMAT-2; MA; MAPs; PDI; CMA; NMDA; ASYN; UPS; SUMO-1; AD; IL; Methamphetamine; ADAM10; PKC; ER; GSK3β; SERT; GDNF; PD; TNF-α; DAQ; DAT; Excitotoxicity; ROS; MAPT; 5-HT; NET; DA; mGluRs
• ISSN: 0753-3322; 1950-6007
• DOI: 10.1016/j.biopha.2022.113591

Methamphetamine (MA) is a extremely addictive psychostimulant drug with a significant abuse potential. Long-term MA exposure can induce neurotoxic effects through oxidative stress, mitochondrial functional impairment, endoplasmic reticulum stress, the activation of astrocytes and microglial cells, axonal transport barriers, autophagy, and apoptosis. However, the molecular and cellular mechanisms underlying MA-induced neurotoxicity remain unclear. MA abuse increases the chances of developing neurotoxic conditions such as Parkinson’s disease (PD), Alzheimer’s disease (AD) and other neurotoxic diseases. MA increases the risk of PD by increasing the expression of alpha-synuclein (ASYN). Furthermore, MA abuse is linked to high chances of developing AD and subsequent neurodegeneration due to biological variations in the brain region or genetic and epigenetic variations. To date, there is no Food and Drug Administration (FDA)-approved therapy for MA-induced neurotoxicity, although many studies are being conducted to develop effective therapeutic strategies. Most current studies are now focused on developing therapies to diminish the neurotoxic effects of MA, based on the underlying mechanism of neurotoxicity. This review article highlights current research on several therapeutic techniques targeting multiple pathways to reduce the neurotoxic effects of MA in the brain, as well as the putative mechanism of MA-induced neurotoxicity. [Display omitted] •Methamphetamine abuse is linked to increased risk of neurotoxic diseases.•There is no FDA approved therapy for methamphetamine-induced neurotoxicity till date.•Targeting multiple pathways can reduce neurotoxic effects of methamphetamine.•Focuses are now on the development of therapy for reducing MA-induced neurotoxicity.