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神经退行性疾病中的生化与分子途径:综合视角

Biochemical and Molecular Pathways in Neurodegenerative Diseases: An Integrated View.

作者信息

Sanghai Nitesh, Tranmer Geoffrey K

机构信息

College of Pharmacy, Rady Faculty of Health Science, University of Manitoba, Winnipeg, MB R3E 0T5, Canada.

Department of Chemistry, Faculty of Science, University of Manitoba, Winnipeg, MB R3T 2N2, Canada.

出版信息

Cells. 2023 Sep 20;12(18):2318. doi: 10.3390/cells12182318.

Abstract

Neurodegenerative diseases (NDDs) like Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS) are defined by a myriad of complex aetiologies. Understanding the common biochemical molecular pathologies among NDDs gives an opportunity to decipher the overlapping and numerous cross-talk mechanisms of neurodegeneration. Numerous interrelated pathways lead to the progression of neurodegeneration. We present evidence from the past pieces of literature for the most usual global convergent hallmarks like ageing, oxidative stress, excitotoxicity-induced calcium butterfly effect, defective proteostasis including chaperones, autophagy, mitophagy, and proteosome networks, and neuroinflammation. Herein, we applied a holistic approach to identify and represent the shared mechanism across NDDs. Further, we believe that this approach could be helpful in identifying key modulators across NDDs, with a particular focus on AD, PD, and ALS. Moreover, these concepts could be applied to the development and diagnosis of novel strategies for diverse NDDs.

摘要

像阿尔茨海默病(AD)、帕金森病(PD)和肌萎缩侧索硬化症(ALS)这样的神经退行性疾病(NDDs)是由无数复杂的病因所定义的。了解神经退行性疾病之间常见的生化分子病理学,为解读神经退行性变中重叠且众多的相互作用机制提供了契机。众多相互关联的途径导致神经退行性变的进展。我们展示了以往文献中关于最常见的全局性趋同特征的证据,如衰老、氧化应激、兴奋性毒性诱导的钙蝴蝶效应、包括分子伴侣、自噬、线粒体自噬和蛋白酶体网络在内的蛋白稳态缺陷,以及神经炎症。在此,我们采用一种整体方法来识别和呈现神经退行性疾病之间的共同机制。此外,我们认为这种方法有助于识别神经退行性疾病的关键调节因子,尤其关注阿尔茨海默病、帕金森病和肌萎缩侧索硬化症。而且,这些概念可应用于多种神经退行性疾病新策略的开发和诊断。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a15d/10527779/6e12e4c19c1c/cells-12-02318-g001.jpg

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