Rahman Md Ataur, Rahman M D Hasanur, Mamun-Or-Rashid A N M, Hwang Hongik, Chung Sooyoung, Kim Bonglee, Rhim Hyewhon
Department of Pathology, College of Korean Medicine, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Korea.
Korean Medicine-Based Drug Repositioning Cancer Research Center, College of Korean Medicine, Kyung Hee University, 1-5, Hoegidong, Dongdaemungu, Seoul 02447, Korea.
Biomedicines. 2022 Apr 29;10(5):1027. doi: 10.3390/biomedicines10051027.
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.
阿尔茨海默病（AD）是世界上最常见的神经退行性疾病之一，其特征是记忆功能障碍以及在包括海马体和皮质在内的多个脑区形成tau蛋白和β淀粉样蛋白（Aβ）聚集体。涉及tau蛋白过度磷酸化、纤维状Aβ和神经原纤维缠结（NFTs）的老年斑形成被用作AD的病理标志物，并最终产生聚集或错误折叠的蛋白质。重要的是，已经发现无法降解这些易于聚集的蛋白质会导致病理后果，如突触损伤、细胞毒性、神经元萎缩以及与AD相关的记忆缺陷。最近，越来越多的证据表明自噬途径作为一种核心的细胞保护系统，在预防聚集或错误折叠蛋白质诱导的毒性方面发挥作用。此外，还发现与AD相关的蛋白聚集体可以通过自噬途径，即通过自噬体与溶酶体融合被选择性降解，这被称为聚集体自噬。因此，调节自噬是调节与AD相关的聚集体形成的一种有效方法。本综述重点介绍了天然化合物和小分子作为通过聚集体自噬预防和治疗AD的潜在治疗方法的应用方面的最新进展。
