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Trilateral association of autophagy, mTOR and Alzheimer’s disease: Potential pathway in the development for Alzheimer’s disease therapy

The primary and considerable weakening event affecting elderly individuals is age-dependent cognitive decline and dementia. Alzheimer’s disease (AD) is the chief cause of progressive dementia, and it is characterized by irreparable loss of cognitive abilities, forming senile plaques having Amyloid B...

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Autores principales: Subramanian, Arunkumar, Tamilanban, T., Alsayari, Abdulrhman, Ramachawolran, Gobinath, Wong, Ling Shing, Sekar, Mahendran, Gan, Siew Hua, Subramaniyan, Vetriselvan, Chinni, Suresh V., Izzati Mat Rani, Nur Najihah, Suryadevara, Nagaraja, Wahab, Shadma
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9817151/
https://www.ncbi.nlm.nih.gov/pubmed/36618946
http://dx.doi.org/10.3389/fphar.2022.1094351
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author Subramanian, Arunkumar
Tamilanban, T.
Alsayari, Abdulrhman
Ramachawolran, Gobinath
Wong, Ling Shing
Sekar, Mahendran
Gan, Siew Hua
Subramaniyan, Vetriselvan
Chinni, Suresh V.
Izzati Mat Rani, Nur Najihah
Suryadevara, Nagaraja
Wahab, Shadma
author_facet Subramanian, Arunkumar
Tamilanban, T.
Alsayari, Abdulrhman
Ramachawolran, Gobinath
Wong, Ling Shing
Sekar, Mahendran
Gan, Siew Hua
Subramaniyan, Vetriselvan
Chinni, Suresh V.
Izzati Mat Rani, Nur Najihah
Suryadevara, Nagaraja
Wahab, Shadma
author_sort Subramanian, Arunkumar
collection PubMed
description The primary and considerable weakening event affecting elderly individuals is age-dependent cognitive decline and dementia. Alzheimer’s disease (AD) is the chief cause of progressive dementia, and it is characterized by irreparable loss of cognitive abilities, forming senile plaques having Amyloid Beta (Aβ) aggregates and neurofibrillary tangles with considerable amounts of tau in affected hippocampus and cortex regions of human brains. AD affects millions of people worldwide, and the count is showing an increasing trend. Therefore, it is crucial to understand the underlying mechanisms at molecular levels to generate novel insights into the pathogenesis of AD and other cognitive deficits. A growing body of evidence elicits the regulatory relationship between the mammalian target of rapamycin (mTOR) signaling pathway and AD. In addition, the role of autophagy, a systematic degradation, and recycling of cellular components like accumulated proteins and damaged organelles in AD, is also pivotal. The present review describes different mechanisms and signaling regulations highlighting the trilateral association of autophagy, the mTOR pathway, and AD with a description of inhibiting drugs/molecules of mTOR, a strategic target in AD. Downregulation of mTOR signaling triggers autophagy activation, degrading the misfolded proteins and preventing the further accumulation of misfolded proteins that inhibit the progression of AD. Other target mechanisms such as autophagosome maturation, and autophagy-lysosomal pathway, may initiate a faulty autophagy process resulting in senile plaques due to defective lysosomal acidification and alteration in lysosomal pH. Hence, the strong link between mTOR and autophagy can be explored further as a potential mechanism for AD therapy.
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spelling pubmed-98171512023-01-07 Trilateral association of autophagy, mTOR and Alzheimer’s disease: Potential pathway in the development for Alzheimer’s disease therapy Subramanian, Arunkumar Tamilanban, T. Alsayari, Abdulrhman Ramachawolran, Gobinath Wong, Ling Shing Sekar, Mahendran Gan, Siew Hua Subramaniyan, Vetriselvan Chinni, Suresh V. Izzati Mat Rani, Nur Najihah Suryadevara, Nagaraja Wahab, Shadma Front Pharmacol Pharmacology The primary and considerable weakening event affecting elderly individuals is age-dependent cognitive decline and dementia. Alzheimer’s disease (AD) is the chief cause of progressive dementia, and it is characterized by irreparable loss of cognitive abilities, forming senile plaques having Amyloid Beta (Aβ) aggregates and neurofibrillary tangles with considerable amounts of tau in affected hippocampus and cortex regions of human brains. AD affects millions of people worldwide, and the count is showing an increasing trend. Therefore, it is crucial to understand the underlying mechanisms at molecular levels to generate novel insights into the pathogenesis of AD and other cognitive deficits. A growing body of evidence elicits the regulatory relationship between the mammalian target of rapamycin (mTOR) signaling pathway and AD. In addition, the role of autophagy, a systematic degradation, and recycling of cellular components like accumulated proteins and damaged organelles in AD, is also pivotal. The present review describes different mechanisms and signaling regulations highlighting the trilateral association of autophagy, the mTOR pathway, and AD with a description of inhibiting drugs/molecules of mTOR, a strategic target in AD. Downregulation of mTOR signaling triggers autophagy activation, degrading the misfolded proteins and preventing the further accumulation of misfolded proteins that inhibit the progression of AD. Other target mechanisms such as autophagosome maturation, and autophagy-lysosomal pathway, may initiate a faulty autophagy process resulting in senile plaques due to defective lysosomal acidification and alteration in lysosomal pH. Hence, the strong link between mTOR and autophagy can be explored further as a potential mechanism for AD therapy. Frontiers Media S.A. 2022-12-22 /pmc/articles/PMC9817151/ /pubmed/36618946 http://dx.doi.org/10.3389/fphar.2022.1094351 Text en Copyright © 2022 Subramanian, Tamilanban, Alsayari, Ramachawolran, Wong, Sekar, Gan, Subramaniyan, Chinni, Izzati Mat Rani, Suryadevara and Wahab. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Subramanian, Arunkumar
Tamilanban, T.
Alsayari, Abdulrhman
Ramachawolran, Gobinath
Wong, Ling Shing
Sekar, Mahendran
Gan, Siew Hua
Subramaniyan, Vetriselvan
Chinni, Suresh V.
Izzati Mat Rani, Nur Najihah
Suryadevara, Nagaraja
Wahab, Shadma
Trilateral association of autophagy, mTOR and Alzheimer’s disease: Potential pathway in the development for Alzheimer’s disease therapy
title Trilateral association of autophagy, mTOR and Alzheimer’s disease: Potential pathway in the development for Alzheimer’s disease therapy
title_full Trilateral association of autophagy, mTOR and Alzheimer’s disease: Potential pathway in the development for Alzheimer’s disease therapy
title_fullStr Trilateral association of autophagy, mTOR and Alzheimer’s disease: Potential pathway in the development for Alzheimer’s disease therapy
title_full_unstemmed Trilateral association of autophagy, mTOR and Alzheimer’s disease: Potential pathway in the development for Alzheimer’s disease therapy
title_short Trilateral association of autophagy, mTOR and Alzheimer’s disease: Potential pathway in the development for Alzheimer’s disease therapy
title_sort trilateral association of autophagy, mtor and alzheimer’s disease: potential pathway in the development for alzheimer’s disease therapy
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9817151/
https://www.ncbi.nlm.nih.gov/pubmed/36618946
http://dx.doi.org/10.3389/fphar.2022.1094351
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