Jeffery Natasha, Mock Phooi Yan, Yang Kun, Tham Chau Ling, Israf Daud Ahmad, Li Hongyuan, Wang Xiaohui, Lam Kok Wai
Centre for Drug and Herbal Development, Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia.
Department of Biomedical Science, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Malaysia.
Future Med Chem. 2025 Jan;17(2):237-257. doi: 10.1080/17568919.2024.2447226. Epub 2024 Dec 27.
Methamphetamine (METH) is a highly addictive illicit psychostimulant with a significant annual fatality rate. Emerging studies highlight its role in neuroinflammation and a range of neurological disorders. This review examines the current landscape of potential drug targets for managing neuroinflammation in METH use disorders (MUDs), with a particular focus on the rationale behind targeting Toll-like receptor 4 (TLR4), the NLR family pyrin domain containing 3 (NLRP3) inflammasome, and other promising targets. Given the multifactorial neurological effects of METH, including cognitive impairment and neurodegeneration, addressing METH-induced neuroinflammation has shown considerable promise in partially mitigating the damaging effects on the central nervous system and improving behavioral outcomes. This article provides an overview of the existing understanding while charting a promising path forward for developing innovative MUD treatments, focusing on neuroinflammation as a therapeutic target. Targeting neuroinflammation in METH-induced neurological disorders shows significant promise in mitigating cognitive impairment and neurodegeneration, offering a potential therapeutic strategy for improving outcomes in MUD. While challenges remain in optimizing treatments, ongoing research into combination therapies, novel drug delivery systems, and neuroprotective agents suggests a positive outlook for more effective interventions.
甲基苯丙胺(METH)是一种极易成瘾的非法精神兴奋剂,年死亡率颇高。新兴研究凸显了其在神经炎症及一系列神经系统疾病中的作用。本综述探讨了在甲基苯丙胺使用障碍(MUDs)中管理神经炎症的潜在药物靶点的现状,特别关注靶向Toll样受体4(TLR4)、含NLR家族吡啶结构域3(NLRP3)炎性小体及其他有前景靶点的理论依据。鉴于METH具有多因素的神经学效应,包括认知障碍和神经退行性变,解决METH诱导的神经炎症在部分减轻对中枢神经系统的损害作用及改善行为结果方面已显示出相当大的前景。本文概述了现有认识,同时为开发创新的MUD治疗方法绘制了一条充满希望的前进道路,重点是将神经炎症作为治疗靶点。针对METH诱导的神经系统疾病中的神经炎症在减轻认知障碍和神经退行性变方面显示出巨大前景,为改善MUD的治疗结果提供了一种潜在的治疗策略。虽然在优化治疗方面仍存在挑战,但对联合疗法、新型药物递送系统和神经保护剂的持续研究为更有效的干预措施带来了积极的前景。