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帕金森病中的初级纤毛:在信号通路、基因、线粒体功能缺陷及黑质多巴胺能神经元中的综合作用

Primary cilia in Parkinson's disease: summative roles in signaling pathways, genes, defective mitochondrial function, and substantia nigra dopaminergic neurons.

作者信息

Tian Zijiao, Zhang Yixin, Xu Jing, Yang Qianwen, Hu Die, Feng Jing, Gai Cong

机构信息

Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China.

College of Acupuncture and Massage, Beijing University of Chinese Medicine, Beijing, China.

出版信息

Front Aging Neurosci. 2024 Sep 18;16:1451655. doi: 10.3389/fnagi.2024.1451655. eCollection 2024.

Abstract

Primary cilia (PC) are microtubules-based, independent antennal-like sensory organelles, that are seen in most vertebrate cells of different types, including astrocytes and neurons. They send signals to cells to control many physiological and cellular processes by detecting changes in the extracellular environment. Parkinson's disease (PD), a neurodegenerative disease that progresses over time, is primarily caused by a gradual degradation of the dopaminergic pathway in the striatum nigra, which results in a large loss of neurons in the substantia nigra compact (SNpc) and a depletion of dopamine (DA). PD samples have abnormalities in the structure and function of PC. The alterations contribute to the cause, development, and recovery of PD via influencing signaling pathways (SHH, Wnt, Notch-1, α-syn, and TGFβ), genes (MYH10 and LRRK2), defective mitochondrial function, and substantia nigra dopaminergic neurons. Thus, restoring the normal structure and physiological function of PC and neurons in the brain are effective treatment for PD. This review summarizes the function of PC in neurodegenerative diseases and explores the pathological mechanisms caused by PC alterations in PD, in order to provide references and ideas for future research.

摘要

原发性纤毛(PC)是基于微管的、类似触角的独立感觉细胞器,可见于包括星形胶质细胞和神经元在内的大多数不同类型的脊椎动物细胞中。它们通过检测细胞外环境的变化向细胞发送信号,以控制许多生理和细胞过程。帕金森病(PD)是一种随时间推移而进展的神经退行性疾病,主要由黑质纹状体多巴胺能通路的逐渐退化引起,这导致黑质致密部(SNpc)大量神经元丢失和多巴胺(DA)耗竭。PD样本中PC的结构和功能存在异常。这些改变通过影响信号通路(SHH、Wnt、Notch-1、α-突触核蛋白和TGFβ)、基因(MYH10和LRRK2)、线粒体功能缺陷以及黑质多巴胺能神经元,对PD的病因、发展和恢复产生影响。因此,恢复大脑中PC和神经元的正常结构和生理功能是治疗PD的有效方法。本综述总结了PC在神经退行性疾病中的功能,并探讨了PD中PC改变引起的病理机制,以便为未来的研究提供参考和思路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ad57/11447156/6e5cec97c224/fnagi-16-1451655-g001.jpg

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