title: Mammalian target of rapamycin: a valid therapeutic target through the autophagy pathway for Alzheimer's disease?
abstract: Autophagy plays a critical role in multiple pathological lesions of Alzheimer's disease (AD), such as the formation of amyloid plaques from amyloid-β (Aβ) production and accumulation via dysregulating amyloid precursor protein turnover and enhancing the activity of β- and/or γ-secretases, intraneuronal neurofibrillary tangles (NFT) because of tau hyperphosphorylation, and neuronal apoptosis. Dysfunction of the autophagy-lysosome system also contributes to Aβ accumulation and the formation of tau oligomers and insoluble aggregates, because induction of autophagy enhances the clearance of both soluble and aggregated forms of Aβ and tau proteins. The mammalian target of rapamycin (mTOR) pathway plays a central role in controlling protein homeostasis and negatively regulates autophagy. Inhibition of mTOR by rapamycin improves cognitive deficits and rescues Aβ pathology and NFTs by increasing autophagy. Several mTOR signaling components may be potential biomarkers of cognitive impairment in the clinical diagnosis of AD. Thus, mTOR-related agents through the control of autophagy-lysosome protein degradation are emerging as an important therapeutic target for AD.
authors.affiliation: Department of Neurology, The Affiliated Hospital of Guangdong Medical College, Zhanjiang, Guangdong, China. caizhiyou2212@gmail.com
authors.forename: Zhiyou
authors.initials: Z
authors.lastname: Cai
authors.forename: Bin
authors.initials: B
authors.lastname: Zhao
authors.forename: Keshen
authors.initials: K
authors.lastname: Li
authors.forename: Liangqing
authors.initials: L
authors.lastname: Zhang
authors.forename: Chunhua
authors.initials: C
authors.lastname: Li
authors.forename: Sohel H
authors.initials: SH
authors.lastname: Quazi
authors.forename: Yan
authors.initials: Y
authors.lastname: Tan
mesh_terms: D000544:Alzheimer Disease / Q000150:complications / Q000188:drug therapy / Q000378:metabolism*; D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D000818:Animals; D001343:Autophagy / Q000187:drug effects / Q000502:physiology*; D003072:Cognition Disorders / Q000188:drug therapy; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology / Q000627:therapeutic use; D016874:Neurofibrillary Tangles / Q000187:drug effects / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D020123:Sirolimus / Q000494:pharmacology / Q000627:therapeutic use; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D016564:Amyloid beta-Protein Precursor; D007166:Immunosuppressive Agents; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D053829:Amyloid Precursor Protein Secretases; D020123:Sirolimus