mTOR signaling and Alzheimer's disease: What we know and where we are?

Autor: Davoody S; Student Research Committee, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran., Asgari Taei A; Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran., Khodabakhsh P; Department of Neurophysiology, Institute of Physiology, Eberhard Karls University of Tübingen, Tübingen, Germany., Dargahi L; Neurobiology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Jazyk: angličtina
Zdroj: CNS neuroscience & therapeutics [CNS Neurosci Ther] 2024 Apr; Vol. 30 (4), pp. e14463. Date of Electronic Publication: 2023 Sep 18.
DOI: 10.1111/cns.14463
Abstrakt: Despite the great body of research done on Alzheimer's disease, the underlying mechanisms have not been vividly investigated. To date, the accumulation of amyloid-beta plaques and tau tangles constitutes the hallmark of the disease; however, dysregulation of the mammalian target of rapamycin (mTOR) seems to be significantly involved in the pathogenesis of the disease as well. mTOR, as a serine-threonine protein kinase, was previously known for controlling many cellular functions such as cell size, autophagy, and metabolism. In this regard, mammalian target of rapamycin complex 1 (mTORC1) may leave anti-aging impacts by robustly inhibiting autophagy, a mechanism that inhibits the accumulation of damaged protein aggregate and dysfunctional organelles. Formation and aggregation of neurofibrillary tangles and amyloid-beta plaques seem to be significantly regulated by mTOR signaling. Understanding the underlying mechanisms and connection between mTOR signaling and AD may suggest conducting clinical trials assessing the efficacy of rapamycin, as an mTOR inhibitor drug, in managing AD or may help develop other medications. In this literature review, we aim to elaborate mTOR signaling network mainly in the brain, point to gaps of knowledge, and define how and in which ways mTOR signaling can be connected with AD pathogenesis and symptoms.
(© 2023 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)
Databáze: MEDLINE
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