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Modulatory Effects of Autophagy on APP Processing as a Potential Treatment Target for Alzheimer’s Disease

Alzheimer’s disease (AD) is characterized by the formation of intracellular aggregate composed of heavily phosphorylated tau protein and extracellular deposit of amyloid-β (Aβ) plaques derived from proteolysis cleavage of amyloid precursor protein (APP). Autophagy refers to the lysosomal-mediated de...

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Autores principales: Rahman, Md. Ataur, Rahman, Md Saidur, Rahman, MD. Hasanur, Rasheduzzaman, Mohammad, Mamun-Or-Rashid, ANM, Uddin, Md Jamal, Rahman, Md Rezanur, Hwang, Hongik, Pang, Myung-Geol, Rhim, Hyewhon
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7824196/
https://www.ncbi.nlm.nih.gov/pubmed/33374126
http://dx.doi.org/10.3390/biomedicines9010005
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author Rahman, Md. Ataur
Rahman, Md Saidur
Rahman, MD. Hasanur
Rasheduzzaman, Mohammad
Mamun-Or-Rashid, ANM
Uddin, Md Jamal
Rahman, Md Rezanur
Hwang, Hongik
Pang, Myung-Geol
Rhim, Hyewhon
author_facet Rahman, Md. Ataur
Rahman, Md Saidur
Rahman, MD. Hasanur
Rasheduzzaman, Mohammad
Mamun-Or-Rashid, ANM
Uddin, Md Jamal
Rahman, Md Rezanur
Hwang, Hongik
Pang, Myung-Geol
Rhim, Hyewhon
author_sort Rahman, Md. Ataur
collection PubMed
description Alzheimer’s disease (AD) is characterized by the formation of intracellular aggregate composed of heavily phosphorylated tau protein and extracellular deposit of amyloid-β (Aβ) plaques derived from proteolysis cleavage of amyloid precursor protein (APP). Autophagy refers to the lysosomal-mediated degradation of cytoplasmic constituents, which plays a critical role in maintaining cellular homeostasis. Importantly, recent studies reported that dysregulation of autophagy is associated in the pathogenesis of AD, and therefore, autophagy modulation has gained attention as a promising approach to treat AD pathogenesis. In AD, both the maturation of autolysosomes and its retrograde transports have been obstructed, which causes the accumulation of autophagic vacuoles and eventually leads to degenerating and dystrophic neurites function. However, the mechanism of autophagy modulation in APP processing and its pathogenesis have not yet been fully elucidated in AD. In the early stage of AD, APP processing and Aβ accumulation-mediated autophagy facilitate the removal of toxic protein aggregates via mTOR-dependent and -independent pathways. In addition, a number of autophagy-related genes (Atg) and APP are thought to influence the development of AD, providing a bidirectional link between autophagy and AD pathology. In this review, we summarized the current observations related to autophagy regulation and APP processing in AD, focusing on their modulation associated with the AD progression. Moreover, we emphasizes the application of small molecules and natural compounds to modulate autophagy for the removal and clearance of APP and Aβ deposits in the pathological condition of AD.
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spelling pubmed-78241962021-01-24 Modulatory Effects of Autophagy on APP Processing as a Potential Treatment Target for Alzheimer’s Disease Rahman, Md. Ataur Rahman, Md Saidur Rahman, MD. Hasanur Rasheduzzaman, Mohammad Mamun-Or-Rashid, ANM Uddin, Md Jamal Rahman, Md Rezanur Hwang, Hongik Pang, Myung-Geol Rhim, Hyewhon Biomedicines Review Alzheimer’s disease (AD) is characterized by the formation of intracellular aggregate composed of heavily phosphorylated tau protein and extracellular deposit of amyloid-β (Aβ) plaques derived from proteolysis cleavage of amyloid precursor protein (APP). Autophagy refers to the lysosomal-mediated degradation of cytoplasmic constituents, which plays a critical role in maintaining cellular homeostasis. Importantly, recent studies reported that dysregulation of autophagy is associated in the pathogenesis of AD, and therefore, autophagy modulation has gained attention as a promising approach to treat AD pathogenesis. In AD, both the maturation of autolysosomes and its retrograde transports have been obstructed, which causes the accumulation of autophagic vacuoles and eventually leads to degenerating and dystrophic neurites function. However, the mechanism of autophagy modulation in APP processing and its pathogenesis have not yet been fully elucidated in AD. In the early stage of AD, APP processing and Aβ accumulation-mediated autophagy facilitate the removal of toxic protein aggregates via mTOR-dependent and -independent pathways. In addition, a number of autophagy-related genes (Atg) and APP are thought to influence the development of AD, providing a bidirectional link between autophagy and AD pathology. In this review, we summarized the current observations related to autophagy regulation and APP processing in AD, focusing on their modulation associated with the AD progression. Moreover, we emphasizes the application of small molecules and natural compounds to modulate autophagy for the removal and clearance of APP and Aβ deposits in the pathological condition of AD. MDPI 2020-12-24 /pmc/articles/PMC7824196/ /pubmed/33374126 http://dx.doi.org/10.3390/biomedicines9010005 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Rahman, Md. Ataur
Rahman, Md Saidur
Rahman, MD. Hasanur
Rasheduzzaman, Mohammad
Mamun-Or-Rashid, ANM
Uddin, Md Jamal
Rahman, Md Rezanur
Hwang, Hongik
Pang, Myung-Geol
Rhim, Hyewhon
Modulatory Effects of Autophagy on APP Processing as a Potential Treatment Target for Alzheimer’s Disease
title Modulatory Effects of Autophagy on APP Processing as a Potential Treatment Target for Alzheimer’s Disease
title_full Modulatory Effects of Autophagy on APP Processing as a Potential Treatment Target for Alzheimer’s Disease
title_fullStr Modulatory Effects of Autophagy on APP Processing as a Potential Treatment Target for Alzheimer’s Disease
title_full_unstemmed Modulatory Effects of Autophagy on APP Processing as a Potential Treatment Target for Alzheimer’s Disease
title_short Modulatory Effects of Autophagy on APP Processing as a Potential Treatment Target for Alzheimer’s Disease
title_sort modulatory effects of autophagy on app processing as a potential treatment target for alzheimer’s disease
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7824196/
https://www.ncbi.nlm.nih.gov/pubmed/33374126
http://dx.doi.org/10.3390/biomedicines9010005
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