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糖尿病、阿尔茨海默病和帕金森病发病机制中糖基化与肠道微生物的共同作用

Communal interaction of glycation and gut microbes in diabetes mellitus, Alzheimer's disease, and Parkinson's disease pathogenesis.

作者信息

Patil Rahul Shivaji, Tupe Rashmi Santosh

机构信息

Vascular Biology Center, Medical College of Georgia, Augusta University, Augusta, Georgia, USA.

Symbiosis School of Biological Sciences (SSBS), Symbiosis International (Deemed University) (SIU), Pune, Maharashtra, India.

出版信息

Med Res Rev. 2024 Jan;44(1):365-405. doi: 10.1002/med.21987. Epub 2023 Aug 17.

Abstract

Diabetes and its complications, Alzheimer's disease (AD), and Parkinson's disease (PD) are increasing gradually, reflecting a global threat vis-à-vis expressing the essentiality of a substantial paradigm shift in research and remedial actions. Protein glycation is influenced by several factors, like time, temperature, pH, metal ions, and the half-life of the protein. Surprisingly, most proteins associated with metabolic and neurodegenerative disorders are generally long-lived and hence susceptible to glycation. Remarkably, proteins linked with diabetes, AD, and PD share this characteristic. This modulates protein's structure, aggregation tendency, and toxicity, highlighting renovated attention. Gut microbes and microbial metabolites marked their importance in human health and diseases. Though many scientific shreds of evidence are proposed for possible change and dysbiosis in gut flora in these diseases, very little is known about the mechanisms. Screening and unfolding their functionality in metabolic and neurodegenerative disorders is essential in hunting the gut treasure. Therefore, it is imperative to evaluate the role of glycation as a common link in diabetes and neurodegenerative diseases, which helps to clarify if modulation of nonenzymatic glycation may act as a beneficial therapeutic strategy and gut microbes/metabolites may answer some of the crucial questions. This review briefly emphasizes the common functional attributes of glycation and gut microbes, the possible linkages, and discusses current treatment options and therapeutic challenges.

摘要

糖尿病及其并发症、阿尔茨海默病(AD)和帕金森病(PD)的发病率正在逐渐上升,这反映出全球面临的一种威胁,表明在研究和治疗行动中进行重大范式转变至关重要。蛋白质糖基化受多种因素影响,如时间、温度、pH值、金属离子和蛋白质的半衰期。令人惊讶的是,大多数与代谢和神经退行性疾病相关的蛋白质通常寿命较长,因此易受糖基化影响。值得注意的是,与糖尿病、AD和PD相关的蛋白质都具有这一特征。这会调节蛋白质的结构、聚集倾向和毒性,凸显了新的关注重点。肠道微生物和微生物代谢产物在人类健康和疾病中具有重要意义。尽管有许多科学证据表明这些疾病中肠道菌群可能发生变化和失调,但对其机制却知之甚少。在代谢和神经退行性疾病中筛选并揭示它们的功能对于挖掘肠道宝藏至关重要。因此,必须评估糖基化作为糖尿病和神经退行性疾病共同联系的作用,这有助于阐明非酶糖基化的调节是否可能作为一种有益的治疗策略,以及肠道微生物/代谢产物是否能回答一些关键问题。本综述简要强调了糖基化和肠道微生物的共同功能特性、可能的联系,并讨论了当前的治疗选择和治疗挑战。

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