Journal of Molecular Medicine

, Volume 82, Issue 3, pp 163–174

Linking DJ-1 to neurodegeneration offers novel insights for understanding the pathogenesis of Parkinson’s disease

Review

DOI: 10.1007/s00109-003-0512-1

Cite this article as:
Bonifati, V., Oostra, B.A. & Heutink, P. J Mol Med (2004) 82: 163. doi:10.1007/s00109-003-0512-1

Abstract

Rare monogenic forms of Parkinson’s disease (PD) are promoting our understanding of the molecular pathways involved in the common, non-Mendelian forms of the disease. Here, we focus on PARK7, an autosomal recessive form of early-onset parkinsonism caused by mutations in the DJ-1 gene. We first review the genetics of this form and the rapidly expanding knowledge about the structure and biochemical properties of the DJ-1 protein. We also discuss how DJ-1 dysfunction might lead to neurodegeneration, and the implications of this novel piece of information for the pathogenesis of the common PD forms. Although much work remains to be done to clarify the biology of DJ-1, its proposed activity as a molecular chaperone and/or as oxidative sensor appear intriguing in the light of the current theories on the pathogenesis of PD.

Keywords

Parkinson’s disease Genes Loci PARK7 DJ-1 

Abbreviations

AR

Androgen receptor

DJBP

DJ-1 binding protein

GAPDH

Glyceraldehyde 3-phosphate dehydrogenase

HDAC

Histone deacetylase

PD

Parkinson’s disease

PIAS

Protein inhibitor of activated STAT

STAT

Signal transducers and activators of transcription

SUMO

Small ubiquitin-like modifier

Copyright information

© Springer-Verlag 2004

Authors and Affiliations

  • Vincenzo Bonifati
    • 1
    • 2
  • Ben A. Oostra
    • 1
  • Peter Heutink
    • 3
  1. 1.Department of Clinical GeneticsErasmus MC RotterdamRotterdamThe Netherlands
  2. 2.Department of Neurological SciencesLa Sapienza UniversityRomeItaly
  3. 3.Section Medical Genomics, Department of Human Genetics and Department of Biological PsychologyVU University Medical CenterAmsterdamThe Netherlands