Outlook of PINK1/Parkin signaling in molecular etiology of Parkinson's disease, with insights into Pink1 knockout models

扫码查看

原文链接

万方数据

外文摘要：Parkinson's disease (PD) relates to defective mitochondrial quality control in the dopaminergic motor network. Genetic studies have revealed that PINK1 and Parkin mutations are indicative of a heightened propensity to PD onset,pinpointing mitophagy and inflammation as the culprit pathways involved in neuronal loss in the substantia nigra(SNpc). In a reciprocal manner, LRRK2 functions in the regulation of basal flux and inflammatory responses responsible for PINK1/Parkin-dependent mitophagy activation. Pharmacological intervention in these disease-modifying pathways may facilitate the development of novel PD therapeutics, despite the current lack of an established drug evaluation model. As such, we reviewed the feasibility of employing the versatile global Pink1 knockout (KO) rat model as a self-sufficient, spontaneous PD model for investigating both disease etiology and drug pharmacology. These rats retain clinical features encompassing basal mitophagic flux changes with PD progression. We demonstrate the versatility of this PD rat model based on the incorporation of additional experimental insults to recapitulate the proinflammatory responses observed in PD patients.

作者：

Zhangting Wang、See-Wing Chan、Hui Zhao、Kai-Kei Miu、Wai-Yee Chan

展开 >

作者单位：

School of Biomedical Sciences,Faculty of Medicine,The Chinese University of Hong Kong,Hong Kong SAR,China

Kunming Institute of Zoology-The Chinese University of Hong Kong(KIZ-CUHK)Joint Laboratory of Bioresources and Molecular Research of Common Diseases,Hong Kong SAR,China

Hong Kong Branch of CAS Center for Excellence in Animal Evolution and Genetics,School of Biomedical Sciences,The Chinese University of Hong Kong,Hong Kong SAR,China

Key Laboratory for Regenerative Medicine,Ministry of Education,School of

展开 >

基金：

KIZ-CUHK Joint Lab of Bioresources and Molecular Research of Common DiseasesVC Discretionary Fund provided to the Hong Kong Branch of Chinese Academy of Science Center for Excellence in Animal EvolutiState Key Laboratory CUHK-Jinan MOE Key Laboratory for Regenerative medicine

项目编号：

4750378Acc 86010112622009

出版年：

2023

DOI：

10.24272/j.issn.2095-8137.2022.406

参考文献

引证文献

动物学研究

CSTPCDCSCD

影响因子：0.582

ISSN：0254-5853

年,卷(期)：2023.44(3)

Zhangting Wang,See-Wing Chan,Hui Zhao,et al.Outlook of PINK1/Parkin signaling in molecular etiology of Parkinson's disease, with insights into Pink1 knockout models[J].动物学研究,2023,44(3):559-576.DOI:10.24272/j.issn.2095-8137.2022.406.

参考文献量225