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Journal of Neural Transmission

, Volume 124, Issue 9, pp 1037–1054 | Cite as

Twenty years since the discovery of the parkin gene

  • Nobutaka Hattori
  • Yoshikuni Mizuno
High Impact Review in Neuroscience, Neurology or Psychiatry - Review Article

Abstract

Nearly 20 years have passed since we identified the causative gene for a familial Parkinson’s disease, parkin (now known as PARK2), in 1998. PARK2 is the most common gene responsible for young-onset Parkinson’s disease. It codes for the protein Parkin RBR E3 ubiquitin-protein ligase (PARK2), which directly links to the ubiquitin-proteasome as a ubiquitin ligase. PARK2 is involved in mitophagy, which is a type of autophagy, in collaboration with PTEN-induced putative kinase 1 (PINK1). The PINK1 gene (previously known as PARK6) is also a causative gene for young-onset Parkinson’s disease. Both gene products may be involved in regulating quality control within the mitochondria. The discovery of PARK2 as a cause of young-onset Parkinson’s disease has had a major impact on other neurodegenerative diseases. The involvement of protein degradation systems has been implicated as a common mechanism for neurodegenerative diseases in which inclusion body formation is observed. The discovery of the involvement of PARK2 in Parkinson’s disease focused attention on the involvement of protein degradation systems in neurodegenerative diseases. In this review, we focus on the history of the discovery of PARK2, the clinical phenotypes of patients with PARK2 mutations, and its functional roles.

Keywords

PARK2 parkin Mitophagy Ubiquitin-proteasome pathway Autophagy-lysosome pathway 

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© Springer-Verlag GmbH Austria 2017

Authors and Affiliations

  1. 1.Department of NeurologyJuntendo University School of MedicineTokyoJapan

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