环境神经毒物和衰老诱导的神经退行性变中的 microRNAs 作用。

Role of microRNAs in neurodegeneration induced by environmental neurotoxicants and aging.

机构信息

Developmental Toxicology Division, Systems Toxicology and Health Risk Assessment Group, CSIR- Indian Institute of Toxicology Research (CSIR-IITR), Vishvigyan Bhawan,31 Mahatma Gandhi Marg, Lucknow-226001, Uttar Pradesh, India; Department of Neurological Surgery, School of Medicine, University of Pittsburgh, 200 Lothrop Street, Pittsburgh, Pennsylvania-15213, USA.

Developmental Toxicology Division, Systems Toxicology and Health Risk Assessment Group, CSIR- Indian Institute of Toxicology Research (CSIR-IITR), Vishvigyan Bhawan,31 Mahatma Gandhi Marg, Lucknow-226001, Uttar Pradesh, India; Department of Biochemistry, All India Institute of Medical Sciences (AIIMS), Raebareli, Munsiganj, Raebareli 229405, UP, India.

出版信息

Ageing Res Rev. 2020 Jul;60:101068. doi: 10.1016/j.arr.2020.101068. Epub 2020 Apr 10.

Abstract

The progressive loss of neuronal structure and functions resulting in the death of neurons is considered as neurodegeneration. Environmental toxicants induced degeneration of neurons is accelerated with aging. In adult brains, most of the neurons are post-mitotic, and their loss results in the development of diseases like amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD), Alzheimer's disease (AD), and Huntington's disease (HD). Neurodegenerative diseases have several similarities at the sub-cellular and molecular levels, such as synaptic degeneration, oxidative stress, inflammation, and cognitive decline, which are also known in brain aging. Identification of these similarities at the molecular level offers hope for the development of new therapeutics to ameliorate all neurodegenerative diseases simultaneously. Aging is known as the most strongly associated additive factor in the pathogenesis of neurodegenerative diseases. Studies carried out so far identified several genes, which are responsible for selective degeneration of neurons in different neurodegenerative diseases. Countless efforts have been made in identifying therapeutics for neurodegenerative diseases; however, the discovery of effective therapy remains elusive. Findings made in the last two decades identified microRNAs (miRNAs) as the most potent post-transcription regulatory RNA molecule, which can condition protein levels in the cell and tissue-specific manner. Identification of miRNAs, which regulate both neurotoxicant and aging-associated degeneration of brain cells, raises the possibility that roads leading to aging and neurotoxicant induced neurodegeneration cross at some point. Identification of miRNAs, which are common to aging and neurotoxicant induced neurodegeneration, will help in understanding the complex mechanism of neurodegenerative disease development. In the future, the use of natural miRNAs in vivo in therapy will be able to tackle several issues of aging and neurodegeneration. In the present review, we have provided a summary of findings made on the role of miRNAs in neurodegeneration and explored the common link made by miRNAs between aging and neurotoxicants induced neurodegeneration.

摘要

神经元结构和功能的进行性丧失导致神经元死亡被认为是神经退行性变。环境毒物诱导的神经元变性随着年龄的增长而加速。在成年大脑中,大多数神经元是有丝分裂后神经元,它们的丧失导致肌萎缩侧索硬化症 (ALS)、帕金森病 (PD)、阿尔茨海默病 (AD) 和亨廷顿病 (HD) 等疾病的发展。神经退行性疾病在亚细胞和分子水平上有几个相似之处,如突触变性、氧化应激、炎症和认知能力下降,这些也与大脑衰老有关。在分子水平上识别这些相似之处为开发新的治疗方法来同时改善所有神经退行性疾病提供了希望。衰老被认为是神经退行性疾病发病机制中最强的相关附加因素。迄今为止的研究确定了几个基因,这些基因负责不同神经退行性疾病中神经元的选择性变性。为了寻找神经退行性疾病的治疗方法,人们付出了无数的努力;然而,有效的治疗方法仍然难以捉摸。过去二十年的研究结果确定了 microRNAs (miRNAs) 作为最有效的转录后调节 RNA 分子,可以以细胞和组织特异性的方式调节蛋白质水平。鉴定出调节神经毒性和与衰老相关的脑细胞变性的 miRNAs,增加了导致衰老和神经毒性诱导的神经退行性变的途径在某些点相交的可能性。鉴定出与衰老和神经毒性诱导的神经退行性变都相关的 miRNAs,将有助于理解神经退行性疾病发展的复杂机制。在未来,体内使用天然 miRNAs 进行治疗将能够解决衰老和神经退行性变的几个问题。在本综述中,我们总结了 miRNAs 在神经退行性变中的作用,并探讨了 miRNAs 在衰老和神经毒性诱导的神经退行性变之间建立的共同联系。

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