Neurotoxicity of methamphetamine: Main effects and mechanisms.
Neurotoxicity of methamphetamine: Main effects and mechanisms.
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DOI：
10.1016/j.expneurol.2021.113795
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发表时间：
2021-10
影响因子：
5.3
通讯作者：
Cadet JL
中科院分区：
文献类型：
--
作者：
Jayanthi S;Daiwile AP;Cadet JL
甲基苯丙胺 (METH) 是一种非法精神兴奋剂，在世界各地被滥用。冰毒成瘾也是一个主要的公共卫生问题，滥用大剂量的药物通常会导致严重的神经精神后果，包括烦躁、焦虑、幻觉、偏执和精神病。一些人类甲基苯丙胺使用者还会出现注意力、记忆力和执行能力缺陷。与冰毒相关的神经和精神并发症可能部分与冰毒引起的神经毒性作用有关。这些包括多巴胺能和血清素能功能的改变、神经元凋亡、星形细胞增多和小胶质细胞增生。在这里，我们尽力讨论该药物的一些主要作用，并提出了支持冰毒神经毒性的某些分子和细胞基础的证据。积累的证据表明转录因子的参与、线粒体和内质网 (ER) 发出的死亡途径的激活以及神经炎症机制的作用。了解冰毒引起的神经毒性的分子过程应该有助于开发更好的治疗方法，这些方法也可能有助于减轻或阻止一些符合冰毒使用障碍标准的人使用大剂量药物所产生的生物学后果。
Methamphetamine (METH) is an illicit psychostimulant that is abused throughout the world. METH addiction is also a major public health concern and the abuse of large doses of the drug is often associated with serious neuropsychiatric consequences that may include agitation, anxiety, hallucinations, paranoia, and psychosis. Some human methamphetamine users can also suffer from attention, memory, and executive deficits. METH-associated neurological and psychiatric complications might be related, in part, to METH-induced neurotoxic effects. Those include altered dopaminergic and serotonergic functions, neuronal apoptosis, astrocytosis, and microgliosis. Here we have endeavored to discuss some of the main effects of the drug and have presented the evidence supporting certain of the molecular and cellular bases of METH neurotoxicity. The accumulated evidence suggests the involvement of transcription factors, activation of dealth pathways that emanate from mitochondria and endoplasmic reticulum (ER), and a role for neuroinflammatory mechanisms. Understanding the molecular processes involved in METH induced neurotoxicity should help in developing better therapeutic approaches that might also serve to attenuate or block the biological consequences of use of large doses of the drug by some humans who meet criteria for METH use disorder.
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