自噬
mTORC1型
PI3K/AKT/mTOR通路
雷帕霉素的作用靶点
mTORC2型
神经科学
生物
激酶
西罗莫司
疾病
细胞生物学
信号转导
医学
内科学
生物化学
细胞凋亡
作者
Julian M. Carosi,Timothy J. Sargeant
出处
期刊:Autophagy
[Informa]
日期:2023-02-10
卷期号:19 (8): 2386-2390
被引量:2
标识
DOI:10.1080/15548627.2023.2175569
摘要
In 2019 we summarized work relating to the potential use of rapamycin for treating Alzheimer disease (AD). We considered the commentary necessary because use of rapamycin in people with AD is a very real prospect and we wanted to present a balanced view of the likely consequences of MTOR (mechanistic target of rapamycin kinase) inhibition in the AD brain. We concluded that use of rapamycin, an MTOR inhibitor that increases macroautophagy/autophagy, could hold promise for prevention of AD if used early enough. However, MTOR inhibition appeared ineffectual in resolving existing amyloid pathology in AD mouse models. In this View article, we update these observations with new studies that have used rapamycin in AD models and provide evidence both for and against its use in AD. We also discuss rapamycin in the light of new research that describes rapamycin-induced autophagic stress in the aging brain and autophagic stress as the origin of the amyloid plaque itself. We conclude that rapamycin will have complex effects on the brain in AD. Further, we hypothesize that lysosomal degradative capacity in the brain will likely determine how effective or detrimental rapamycin will be as a treatment of AD.Abbreviations: AD: Alzheimer disease; APP: amyloid beta precursor protein; MAPT/tau: microtubule associated protein tau; MTOR: mechanistic target of rapamycin kinase; MTORC1: mechanistic target of rapamycin kinase complex 1.
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