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

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.

Promising Modulatory Effects of Autophagy on APP Processing as a Potential Treatment for Alzheimer's Disease

“…Mammalian target of rapamycin (mTOR) is an essential serine-threonine protein kinase, comprising mTOR complex 1 (mTORC1) as well as mTOR complex 2 (mTORC2) [20]. mTOR is known as a classical regulator of autophagy and controls vital cellular functions, such as protein translation and cell growth [21,22]. The mTOR activity is closely associated with numerous factors, including chronic stress, starvation, and glucocorticoids.…”

Potential Therapeutic Role of Phytochemicals to Mitigate Mitochondrial Dysfunctions in Alzheimer’s Disease

“…Many phytochemicals have been found to inhibit mTOR signaling, thereby inducing autophagy pathway [6,72]. Polyphenols have also been revealed to inhibit oligomer synthesis and formation in addition to prevent tau hyperphosphorylation and aggregation reduction in vitro and in vivo [73].…”

“…AD shows common symptoms like insanity and leads to morbid state and death in the aged peoples [4]. In both familial and sporadic patterns, AD is characterized by dual unique medical hallmarks: amyloidβ (Aβ) peptide extracellular accumulation in the senile plaques and neurofibrillary tangles (NFTs) intracellular deposition formed through hyperphosphorylation of tau proteins [5,6].…”

Emerging Promise of Cannabinoids for the Management of Pain and Associated Neuropathological Alterations in Alzheimer’s Disease

“…Neuropathological alterations that take place in dementia patients are accountable for changes in the perception of pain ( Van Kooten et al., 2016 ). Though these changes can be common in different forms of dementia, however, scientists are trying to investigate the pain perception and processing in the patients of Alzheimer’s disease (AD), which is characterized by behavioral and cognitive impairments ( Al Mamun et al., 2020b ; Uddin et al., 2020a ; Uddin et al., 2020l ). Neuropathological hallmarks of AD are extracellular accumulations of amyloid beta (Aβ) as well as intracellular accumulations of neurofibrillary tangles (NFTs) that are comprised of hyperphosphorylation of tau ( Uddin et al., 2019 ; Mamun et al., 2020 ; Uddin et al., 2020d ).…”