College of Pharmacy, Keimyung University, 1095 Dalgubeol-daero, Dalseo-Gu, Daegu 42601, Republic of Korea.
Department of Biochemistry, School of Medicine, Keimyung University, Daegu 42601, Republic of Korea.
Biomed Pharmacother. 2022 Oct;154:113591. doi: 10.1016/j.biopha.2022.113591. Epub 2022 Aug 22.
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.
甲基苯丙胺（MA）是一种极具成瘾性的精神兴奋剂，具有显著的滥用潜力。长期 MA 暴露会通过氧化应激、线粒体功能障碍、内质网应激、星形胶质细胞和小胶质细胞的激活、轴突运输障碍、自噬和细胞凋亡引起神经毒性作用。然而，MA 诱导的神经毒性的分子和细胞机制尚不清楚。MA 滥用会增加患神经毒性疾病的风险，如帕金森病（PD）、阿尔茨海默病（AD）和其他神经毒性疾病。MA 通过增加α-突触核蛋白（ASYN）的表达来增加 PD 的风险。此外，由于大脑区域的生物学变化或遗传和表观遗传变化，MA 滥用与 AD 及随后的神经退行性变的高风险相关。迄今为止，尽管正在进行许多研究以开发有效的治疗策略，但美国食品和药物管理局（FDA）尚未批准用于 MA 诱导的神经毒性的治疗方法。目前的大多数研究都集中在开发基于神经毒性潜在机制的疗法，以减轻 MA 的神经毒性作用。本文综述了几种针对多种途径的治疗技术的研究进展，这些技术旨在减轻 MA 在大脑中的神经毒性作用，以及 MA 诱导的神经毒性的可能机制。
