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哺乳动物雷帕霉素靶蛋白(mTOR)通路与神经退行性疾病。

Mammalian target of rapamycin (mTOR) pathways in neurological diseases.

机构信息

Department of Neurology and the Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO 63110, USA.

出版信息

Biomed J. 2013 Mar-Apr;36(2):40-50. doi: 10.4103/2319-4170.110365.

Abstract

The mammalian target of rapamycin (mTOR) pathway is an essential cellular signaling pathway involved in a number of important physiological functions, including cell growth, proliferation, metabolism, protein synthesis, and autophagy. Dysregulation of the mTOR pathway has been implicated in the pathophysiology of a number of neurological diseases. Hyperactivation of the mTOR pathway, leading to increased cell growth and proliferation, has been most convincingly shown to stimulate tumor growth in the brain and other organs in the genetic disorder, tuberous sclerosis complex (TSC). In addition, mTOR may also play a role in promoting epileptogenesis or maintaining seizures in TSC, as well as in acquired epilepsies following brain injury. Finally, the mTOR pathway may also be involved in the pathogenesis of cognitive dysfunction and other neurological deficits in developmental disorders and neurodegenerative diseases. mTOR inhibitors, such as rapamycin and its analogs, may represent novel, rational therapies for a variety of neurological disorders.

摘要

哺乳动物雷帕霉素靶蛋白(mTOR)途径是一种重要的细胞信号通路,参与许多重要的生理功能,包括细胞生长、增殖、代谢、蛋白质合成和自噬。mTOR 途径的失调与许多神经疾病的病理生理学有关。mTOR 途径的过度激活导致细胞生长和增殖增加,这在遗传疾病结节性硬化症(TSC)中最令人信服地表明会刺激大脑和其他器官中的肿瘤生长。此外,mTOR 可能在 TSC 中的癫痫发生或维持发作中发挥作用,以及在脑损伤后的获得性癫痫中发挥作用。最后,mTOR 途径也可能参与发育障碍和神经退行性疾病中的认知功能障碍和其他神经缺陷的发病机制。雷帕霉素及其类似物等 mTOR 抑制剂可能代表治疗各种神经疾病的新型合理疗法。

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