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PINK1, Parkin, and Mitochondrial Quality Control: What can we Learn about Parkinson's Disease Pathobiology?

期刊

JOURNAL OF PARKINSONS DISEASE
卷 7, 期 1, 页码 13-29

出版社

IOS PRESS
DOI: 10.3233/JPD-160989

关键词

Parkinson's disease; PINK1; Parkin; ubiquitin; mitochondria; mitophagy

资金

  1. National Institutes of Health (NIH)/National Institute of Neurological Disorders and Stroke (NINDS) [NS085070]
  2. Michael J. Fox Foundation for Parkinson's Research
  3. Foundation for Mitochondrial Medicine
  4. Mayo Clinic Center for Regenerative Medicine (CRM)
  5. Center for Individualized Medicine (CIM)
  6. Center for Biomedical Discovery (CBD)
  7. Marriott Family Foundation
  8. Gerstner Family Career Development Award
  9. American Parkinson Disease Association (APDA)
  10. Younkin Scholar Program
  11. NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE [R01NS085070] Funding Source: NIH RePORTER

向作者/读者索取更多资源

The first clinical description of Parkinson's disease (PD) will embrace its two century anniversary in 2017. For the past 30 years, mitochondrial dysfunction has been hypothesized to play a central role in the pathobiology of this devastating neurodegenerative disease. The identifications of mutations in genes encoding PINK1 (PTEN-induced kinase 1) and Parkin (E3 ubiquitin ligase) in familial PD and their functional association with mitochondrial quality control provided further support to this hypothesis. Recent research focused mainly on their key involvement in the clearance of damaged mitochondria, a process knownas mitophagy. It has become evident that there are many other aspects of this complex regulated, multifaceted pathway that provides neuroprotection. As such, numerous additional factors that impact PINK1/Parkin have already been identified including genes involved in other forms of PD. A great pathogenic overlap amongst different forms of familial, environmental and even sporadic disease is emerging that potentially converges at the level of mitochondrial quality control. Tremendous efforts now seek to further detail the roles and exploit PINK1 and Parkin, their upstream regulators and downstream signaling pathways for future translation. This review summarizes the latest findings on PINK1/Parkin-directed mitochondrial quality control, its integration and cross-talk with other disease factors and pathways as well as the implications for idiopathic PD. In addition, we highlight novel avenues for the development of biomarkers and disease-modifying therapies that are based on a detailed understanding of the PINK1/Parkin pathway.

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