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淀粉样蛋白诱导的神经退行性变:通过聚集组学对健康和病理状态下蛋白质的认识进行全面综述。

Amyloid-induced neurodegeneration: A comprehensive review through aggregomics perception of proteins in health and pathology.

机构信息

Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, Jamia Nagar, New Delhi 110025, India.

Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, Jamia Nagar, New Delhi 110025, India; Department of Biosciences, Jamia Millia Islamia, Jamia Nagar, New Delhi 110025, India.

出版信息

Ageing Res Rev. 2024 Apr;96:102276. doi: 10.1016/j.arr.2024.102276. Epub 2024 Mar 16.

Abstract

Amyloidosis of protein caused by fibrillation and aggregation are some of the most exciting new edges not only in protein sciences but also in molecular medicines. The present review discusses recent advancements in the field of neurodegenerative diseases and therapeutic applications with ongoing clinical trials, featuring new areas of protein misfolding resulting in aggregation. The endogenous accretion of protein fibrils having fibrillar morphology symbolizes the beginning of neuro-disorders. Prognostic amyloidosis is prominent in numerous degenerative infections such as Alzheimer's and Parkinson's disease, Amyotrophic lateral sclerosis (ALS), etc. However, the molecular basis determining the intracellular or extracellular evidence of aggregates, playing a significant role as a causative factor in neurodegeneration is still unclear. Structural conversions and protein self-assembly resulting in the formation of amyloid oligomers and fibrils are important events in the pathophysiology of the disease. This comprehensive review sheds light on the evolving landscape of potential treatment modalities, highlighting the ongoing clinical trials and the potential socio-economic impact of novel therapeutic interventions in the realm of neurodegenerative diseases. Furthermore, many drugs are undergoing different levels of clinical trials that would certainly help in treating these disorders and will surely improve the socio-impact of human life.

摘要

由纤维状和聚集引起的蛋白质淀粉样变性是蛋白质科学和分子医学中最令人兴奋的新领域之一。本综述讨论了神经退行性疾病领域的最新进展以及正在进行的临床试验中的治疗应用,重点介绍了导致聚集的新的蛋白质错误折叠区域。具有纤维状形态的内源性蛋白质原纤维的积累标志着神经紊乱的开始。淀粉样变性在许多退行性感染中很明显,如阿尔茨海默病和帕金森病、肌萎缩性侧索硬化症(ALS)等。然而,确定细胞内或细胞外聚集证据的分子基础,作为神经退行性变的一个重要原因,仍然不清楚。结构转换和蛋白质自组装导致淀粉样寡聚体和纤维的形成是疾病病理生理学中的重要事件。本综述阐明了潜在治疗方法的不断发展的前景,强调了正在进行的临床试验以及神经退行性疾病领域新型治疗干预措施的潜在社会经济影响。此外,许多药物正在进行不同阶段的临床试验,这肯定有助于治疗这些疾病,并将极大地改善人类生活的社会影响。

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