氧化三甲胺在阿尔兹海默病中的研究进展

Research progress of trimethylamine oxide in Alzheimer’s disease

阿尔兹海默症(alzheimer’s disease,AD)是一种影响记忆和认知功能的神经退行性疾病,是导致成年后痴呆的主要原因,该病与多种危险因素相关,其中肠道微生物代谢产物氧化三甲胺(TMAO)最近被确认为AD的潜在危险因素。已经证明TMAO通过各种病理生理途径与AD有关。由于分子拥挤效应,TMAO导致淀粉样β肽和tau蛋白这两种蛋白质聚集。这些蛋白的聚集是AD的关键病理特征。此外,已经发现TMAO可以激活星形胶质细胞和炎性反应。除了分子研究外,动物和人类的研究也支持TMAO与认知功能下降之间存在功能关系。本文对TMAO的产生、以及微生物-肠-脑轴系统进行了全面的讨论,全面总结TMAO与AD之间的关系,包括来自体外、体内和临床研究的新证据。希望这些知识能在不久的将来改善AD的预防和治疗。

Alzheimer's disease(AD) is a neurodegenerative disease that affects memory and cognitive functions,which is a major cause of dementia in adulthood.AD is associated with several risk factors,among which trimethylamine oxide(TMAO),a gut microbial metabolite,has recently been identified as a potential risk factor for it.TMAO has been shown to be associated with AD through various pathophysiological pathways.Due to molecular crowding effects,TMAO leads to the aggregation of two proteins,namely the amyloid beta peptide and tau protein.Their aggregations are a key pathological feature of AD.In addition,TMAO has been found to activate astrocytes and inflammatory responses.In addition to molecular studies,animal and human studies also support a functional relationship between TMAO and cognitive decline.This article comprehensively describes TMAO production,the microbial-gut-brain axis system,and the relationship between TMAO and AD by illustrating latest in vitro,in vivo,and clinical evidences,aiming to improve the prevention and treatment of AD.