Volume 44 Issue 3
May  2023
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Zhangting Wang, See-Wing Chan, Hui Zhao, Kai-Kei Miu, Wai-Yee Chan. Outlook of PINK1/Parkin signaling in molecular etiology of Parkinson’s disease, with insights into Pink1 knockout models. Zoological Research, 2023, 44(3): 559-576. doi: 10.24272/j.issn.2095-8137.2022.406
Citation: Zhangting Wang, See-Wing Chan, Hui Zhao, Kai-Kei Miu, Wai-Yee Chan. Outlook of PINK1/Parkin signaling in molecular etiology of Parkinson’s disease, with insights into Pink1 knockout models. Zoological Research, 2023, 44(3): 559-576. doi: 10.24272/j.issn.2095-8137.2022.406

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

doi: 10.24272/j.issn.2095-8137.2022.406
The authors declare that they have no competing interests.
W.Z. conceptualized, wrote, and edited the manuscript. S.W.C. and K.K.M. assisted in the writing and critical review of the text. H.Z. provided financial support. W.Y.C. conceptualized, designed, edited, and provided financial support. All authors read and approved the final version of the manuscript.
Funds:  The work was supported by the KIZ-CUHK Joint Lab of Bioresources and Molecular Research of Common Diseases (4750378), the VC Discretionary Fund provided to the Hong Kong Branch of Chinese Academy of Science Center for Excellence in Animal Evolution and Genetics (Acc 8601011) and partially by the State Key Laboratory CUHK-Jinan MOE Key Laboratory for Regenerative medicine (2622009)
More Information
  • 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.
  • The authors declare that they have no competing interests.
    W.Z. conceptualized, wrote, and edited the manuscript. S.W.C. and K.K.M. assisted in the writing and critical review of the text. H.Z. provided financial support. W.Y.C. conceptualized, designed, edited, and provided financial support. All authors read and approved the final version of the manuscript.
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