Autophagy Modulation in Aggresome Formation: Emerging Implications and Treatments of Alzheimer’s Disease

Biomedicines

A. N. M. Mamun-Or-Rashid¹  Hyewhon Rhim²  Sooyoung Chung²  Hongik Hwang²  MD. Hasanur Rahman³  Md. Ataur Rahman³  Bonglee Kim³ 

[1] Anti-Aging Medical Research Center and Glycation Stress Research Center, Graduate School of Life and Medical Sciences, Doshisha University, Kyoto 602-8566, Japan;Center for Neuroscience, Brain Science Institute, Korea Institute of Science and Technology (KIST), 5 Hwarang-ro 14-gil, Seongbuk-gu, Seoul 02792, Korea;Department of Pathology, College of Korean Medicine, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Korea;

关键词: Alzheimer’s disease (AD);    aggregation;    autophagy;    aggresome;    autophagosomes;    aggrephagy;   

DOI  :  10.3390/biomedicines10051027

来源: DOAJ

【 摘 要 】

Alzheimer’s disease (AD) is one of the most prevailing neurodegenerative diseases in the world, which is characterized by memory dysfunction and the formation of tau and amyloid β (Aβ) aggregates in multiple brain regions, including the hippocampus and cortex. The formation of senile plaques involving tau hyperphosphorylation, fibrillar Aβ, and neurofibrillary tangles (NFTs) is used as a pathological marker of AD and eventually produces aggregation or misfolded protein. Importantly, it has been found that the failure to degrade these aggregate-prone proteins leads to pathological consequences, such as synaptic impairment, cytotoxicity, neuronal atrophy, and memory deficits associated with AD. Recently, increasing evidence has suggested that the autophagy pathway plays a role as a central cellular protection system to prevent the toxicity induced by aggregation or misfolded proteins. Moreover, it has also been revealed that AD-related protein aggresomes could be selectively degraded by autophagosome and lysosomal fusion through the autophagy pathway, which is known as aggrephagy. Therefore, the regulation of autophagy serve as a useful approach to modulate the formation of aggresomes associated with AD. This review focuses on the recent improvements in the application of natural compounds and small molecules as a potential therapeutic approach for AD prevention and treatment via aggrephagy.

【 授权许可】

Unknown