Poly (ADP-ribose) in the pathogenesis of Parkinson's disease

BMB Rep. 2014 Aug;47(8):424-32. doi: 10.5483/bmbrep.2014.47.8.119.

Abstract

The defining feature of Parkinson's disease is a progressive and selective demise of dopaminergic neurons. A recent report on Parkinson's disease animal model demonstrates that poly (ADP-ribose) (PAR) dependent cell death, also named parthanatos, is accountable for selective dopaminergic neuronal loss. Parthanatos is a programmed necrotic cell death, characterized by PARP1 activation, apoptosis inducing factor (AIF) nuclear translocation, and large scale DNA fragmentation. Besides cell death regulation via interaction with AIF, PAR molecule mediates diverse cellular processes including genomic stability, cell division, transcription, epigenetic regulation, and stress granule formation. In this review, we will discuss the roles of PARP1 activation and PAR molecules in the pathological processes of Parkinson's disease. Potential interaction between PAR molecule and Parkinson's disease protein interactome are briefly introduced. Finally, we suggest promising points of therapeutic intervention in the pathological PAR signaling cascade to halt progression in Parkinson's disease.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Apoptosis
  • Apoptosis Inducing Factor / metabolism
  • DNA Fragmentation
  • Dopaminergic Neurons / metabolism
  • Dopaminergic Neurons / pathology
  • Enzyme Inhibitors / therapeutic use
  • Humans
  • Parkinson Disease / drug therapy
  • Parkinson Disease / metabolism
  • Parkinson Disease / pathology*
  • Poly Adenosine Diphosphate Ribose / metabolism*
  • Poly(ADP-ribose) Polymerase Inhibitors
  • Poly(ADP-ribose) Polymerases / metabolism

Substances

  • Apoptosis Inducing Factor
  • Enzyme Inhibitors
  • Poly(ADP-ribose) Polymerase Inhibitors
  • Poly Adenosine Diphosphate Ribose
  • Poly(ADP-ribose) Polymerases