Multifarious roles of mTOR signaling in cognitive aging and cerebrovascular dysfunction of Alzheimer's disease

Md Sahab Uddin, Md Ataur Rahman, Md Tanvir Kabir, Tapan Behl, Bijo Mathew, Asma Perveen, George E. Barreto, May N. Bin-Jumah, Mohamed M. Abdel-Daim, Ghulam Md Ashraf

Research output: Contribution to journalReview articlepeer-review

Abstract

Age-related cognitive failure is a main devastating incident affecting even healthy people. Alzheimer's disease (AD) is the utmost common form of dementia among the geriatric community. In the pathogenesis of AD, cerebrovascular dysfunction is revealed before the beginning of the cognitive decline. Mounting proof shows a precarious impact of cerebrovascular dysregulation in the development of AD pathology. Recent studies document that the mammalian target of rapamycin (mTOR) acts as a crucial effector of cerebrovascular dysregulation in AD. The mTOR contributes to brain vascular dysfunction and subsequence cerebral blood flow deficits as well as cognitive impairment. Furthermore, mTOR causes the blood–brain barrier (BBB) breakdown in AD models. Inhibition of mTOR hyperactivity protects the BBB integrity in AD. Furthermore, mTOR drives cognitive defect and cerebrovascular dysfunction, which are greatly prevalent in AD, but the central molecular mechanisms underlying these alterations are obscure. This review represents the crucial and current research findings regarding the role of mTOR signaling in cognitive aging and cerebrovascular dysfunction in the pathogenesis of AD.

Original languageEnglish
Pages (from-to)1843-1855
Number of pages13
JournalIUBMB Life
Volume72
Issue number9
DOIs
Publication statusPublished - 1 Sep 2020

Keywords

  • Alzheimer's disease
  • blood–brain barrier
  • cerebrovascular dysfunction
  • cognitive aging
  • mTOR

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