Preprint Review Version 1 Preserved in Portico This version is not peer-reviewed

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

Version 1 : Received: 8 October 2020 / Approved: 9 October 2020 / Online: 9 October 2020 (11:07:53 CEST)

How to cite: Rahman, M.A.; Rahman, M.S.; Rahman, M.H.; Rasheduzzaman, M.; Mamun-Or-Rashid, A.; Uddin, M.J.; Rahman, M.R.; Hwang, H.; Pang, M.; Rhim, H. Promising Modulatory Effects of Autophagy on APP Processing as a Potential Treatment for Alzheimer's Disease. Preprints 2020, 2020100195 (doi: 10.20944/preprints202010.0195.v1). Rahman, M.A.; Rahman, M.S.; Rahman, M.H.; Rasheduzzaman, M.; Mamun-Or-Rashid, A.; Uddin, M.J.; Rahman, M.R.; Hwang, H.; Pang, M.; Rhim, H. Promising Modulatory Effects of Autophagy on APP Processing as a Potential Treatment for Alzheimer's Disease. Preprints 2020, 2020100195 (doi: 10.20944/preprints202010.0195.v1).

Abstract

Autophagy refers to the degradation of cytoplasmic constituents by a lysosomal-mediated pathway, which plays a critical role in maintaining cellular homeostasis. Importantly, dysregulation of autophagy has been implicated in multiple neurodegenerative disorders. Previous studies reported that autophagy affects the processing of amyloid precursor protein (APP), thus stimulating β‐amyloid (Aβ) production in Alzheimer’s disease (AD) eventually. Although the mechanism of autophagy modulation on APP processing and its pathogenesis has not yet been fully elucidated at the molecular level, but modulation of autophagy has received considerable attention as a promising approach for the treatment of AD. In the early stage of AD, Aβ may prompt autophagy to facilitate its removal via mTOR‐independent as well as-dependent pathways. However, a recent study proposed that autophagy processes are not properly regulated as AD continues to progress, and consequently, the production of Aβ tends to accumulate rapidly. Meanwhile, a number of autophagy-related genes (Atg) as well as APP genes are also thought to influence the development of AD, which may serve as a bi‐directional link to autophagy and AD pathology. In this review, we summarized current observations related to autophagy regulation and APP processing, focusing on their dynamic modifications associated with the progression of AD. Recent findings together highlight the essential role of autophagy in the removal and clearance of APP and Aβ deposition in the pathological condition of AD.

Subject Areas

Autophagy; Amyloid precursor protein (APP); β‐amyloid (Aβ); mTOR; Alzheimer’s disease (AD).

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