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

@article{davoody2023mtor,
  title={mTOR signaling and Alzheimer's disease: What we know and where we are?},
  author={Davoody, Samin and Asgari Taei, Afsaneh and Khodabakhsh, Pariya and Dargahi, Leila},
  journal={CNS Neuroscience \& Therapeutics},
  year={2023},
  publisher={Wiley Online Library}
}
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Abstract

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.

Year of Publication
2023
Journal
CNS neuroscience & therapeutics
Date Published
09/2023
ISSN Number
1755-5949
DOI
10.1111/cns.14463
Alternate Journal
CNS Neurosci Ther
PMID
37721413
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