首页|Outlook of PINK1/Parkin signaling in molecular etiology of Parkinson's disease, with insights into Pink1 knockout models
Outlook of PINK1/Parkin signaling in molecular etiology of Parkinson's disease, with insights into Pink1 knockout models
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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.
Parkinson's diseaseMitophagyInflammatory responseGenetic modelPink1 KO rats
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
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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
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