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自噬与不同疾病的关联——治疗方法的最新策略

Autophagy Intertwines with Different Diseases-Recent Strategies for Therapeutic Approaches.

作者信息

Ramesh Janani, Ronsard Larance, Gao Anthony, Venugopal Bhuvarahamurthy

机构信息

Department of Medical Biochemistry, Dr. A.L.M. Post Graduate Institute of Basic Medical Sciences, University of Madras, Chennai 600113, India.

Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.

出版信息

Diseases. 2019 Feb 1;7(1):15. doi: 10.3390/diseases7010015.

Abstract

Autophagy is a regular and substantial "clear-out process" that occurs within the cell and that gets rid of debris that accumulates in membrane-enclosed vacuoles by using enzyme-rich lysosomes, which are filled with acids that degrade the contents of the vacuoles. This machinery is well-connected with many prevalent diseases, including cancer, HIV, and Parkinson's disease. Considering that autophagy is well-known for its significant connections with a number of well-known fatal diseases, a thorough knowledge of the current findings in the field is essential in developing therapies to control the progression rate of diseases. Thus, this review summarizes the critical events comprising autophagy in the cellular system and the significance of its key molecules in manifesting this pathway in various diseases for down- or upregulation. We collectively reviewed the role of autophagy in various diseases, mainly neurodegenerative diseases, cancer, inflammatory diseases, and renal disorders. Here, some collective reports on autophagy showed that this process might serve as a dual performer: either protector or contributor to certain diseases. The aim of this review is to help researchers to understand the role of autophagy-regulating genes encoding functional open reading frames (ORFs) and its connection with diseases, which will eventually drive better understanding of both the progression and suppression of different diseases at various stages. This review also focuses on certain novel therapeutic strategies which have been published in the recent years based on targeting autophagy key proteins and its interconnecting signaling cascades.

摘要

自噬是细胞内发生的一种常规且重要的“清除过程”,它通过富含酶的溶酶体清除积聚在膜包裹的液泡中的碎片,溶酶体中充满了可降解液泡内容物的酸性物质。这一机制与许多常见疾病相关,包括癌症、艾滋病和帕金森病。鉴于自噬因其与许多致命疾病的显著关联而闻名,全面了解该领域的当前研究结果对于开发控制疾病进展速度的疗法至关重要。因此,本综述总结了细胞系统中自噬所包含的关键事件,以及其关键分子在各种疾病中调节该途径(上调或下调)的重要性。我们共同回顾了自噬在各种疾病中的作用,主要是神经退行性疾病、癌症、炎症性疾病和肾脏疾病。在此,一些关于自噬的综合报告表明,这一过程可能具有双重作用:对某些疾病既是保护因素,也是促成因素。本综述的目的是帮助研究人员了解编码功能性开放阅读框(ORF)的自噬调节基因的作用及其与疾病的关联,这最终将有助于更好地理解不同疾病在各个阶段的进展和抑制情况。本综述还重点关注了近年来基于靶向自噬关键蛋白及其相互连接的信号级联反应而发表的某些新型治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c815/6473623/67c85794153e/diseases-07-00015-g001.jpg

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