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

IF 4.1 2区 医学 Q2 GERIATRICS & GERONTOLOGY Frontiers in Aging Neuroscience Pub Date : 2024-09-18 eCollection Date: 2024-01-01 DOI:10.3389/fnagi.2024.1451655
Zijiao Tian, Yixin Zhang, Jing Xu, Qianwen Yang, Die Hu, Jing Feng, Cong Gai
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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.

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帕金森病中的原发性纤毛:在信号通路、基因、线粒体功能缺陷和黑质多巴胺能神经元中的总结性作用。
初级纤毛(PC)是一种以微管为基础的、独立的类似触角的感觉器,存在于大多数不同类型的脊椎动物细胞中,包括星形胶质细胞和神经元。它们通过检测细胞外环境的变化向细胞发送信号,从而控制许多生理和细胞过程。帕金森病(Parkinson's disease,简称 PD)是一种随着时间推移而发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,导致黑质紧密区(SNpc)神经元的大量丢失和多巴胺(DA)的耗竭。帕金森病样本中的 PC 结构和功能都存在异常。这些改变通过影响信号通路(SHH、Wnt、Notch-1、α-syn 和 TGFβ)、基因(MYH10 和 LRRK2)、线粒体功能缺陷和黑质多巴胺能神经元,对帕金森病的病因、发展和康复做出了贡献。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帕金森病的有效方法。本综述总结了PC在神经退行性疾病中的功能,探讨了PC改变在帕金森病中的病理机制,以期为今后的研究提供参考和思路。
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来源期刊
Frontiers in Aging Neuroscience
Frontiers in Aging Neuroscience GERIATRICS & GERONTOLOGY-NEUROSCIENCES
CiteScore
6.30
自引率
8.30%
发文量
1426
期刊介绍: Frontiers in Aging Neuroscience is a leading journal in its field, publishing rigorously peer-reviewed research that advances our understanding of the mechanisms of Central Nervous System aging and age-related neural diseases. Specialty Chief Editor Thomas Wisniewski at the New York University School of Medicine is supported by an outstanding Editorial Board of international researchers. This multidisciplinary open-access journal is at the forefront of disseminating and communicating scientific knowledge and impactful discoveries to researchers, academics, clinicians and the public worldwide.
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