Rapamycin, Autophagy, and Alzheimer's Disease.
Alzheimer's disease (AD) is a neurodegenerative disorder characterized by cognitive impairment and multiple pathological lesions. At the molecular level, AD is characterized by overt amyloid β (Aβ) production and tau hyper-phosphorylation. Hence, pharmacological agents that can attenuate Aβ accumulation and tau hyper-phosphorylation have potential promise for treatment of AD. Rapamycin, an inhibitor of mammalian target of rapamycin (mTOR), is believed to be one of such pharmacological agents. It is neuroprotective in neurodegenerative diseases and its primary action is thought to be via enhancement of autophagy, a biological process that not only facilitates the clearance of mutant proteins but also significantly reduces the build-up of toxic protein aggregates such as Aβ. Since rapamycin enhancement of autophagy has been associated with abrogation of AD pathological processes such as clearance of Aβ and neurofibrillary tangles (NTFs) as well as reduction of tau hyper-phosphorylation and improvement of cognition, rapamycin is emerging as a potential therapeutic compound for AD.
['Cai|Zhiyou|Z|', 'Yan|Liang-Jun|LJ|']
rapamycin autophagy mTOR Alzheimer’s disease neuroinflammation oxidative stress synaptic impairment