Dopamine oxidation mediates mitochondrial and lysosomal dysfunction in Parkinson’s disease

Mitochondrial and lysosomal dysfunction have been implicated in substantia nigra dopaminergic neurodegeneration in Parkinson's disease (PD), but how these pathways are linked in human neurons remains unclear. Here we studied dopaminergic neurons derived from patients with idiopathic and familial PD. We identified a time-dependent pathological cascade beginning with mitochondrial oxidant stress leading to oxidized dopamine accumulation and ultimately resulting in reduced glucocerebrosidase enzymatic activity, lysosomal dysfunction, and α-synuclein accumulation. This toxic cascade was observed in human, but not in mouse, PD neurons at least in part because of species-specific differences in dopamine metabolism.…

• MJ
  Michael J. Fox Foundation for Parkinson's Research

  Award: award346546
• SM
  Spinal Muscular Atrophy Foundation

  Award: award301007
• LT
  Les Turner ALS Foundation

  Award: award301005
• JF
  JPB Foundation

  Award: award346543
• TA
  Target ALS

  Award: award301006
• IF
  IDP Foundation

  Award: award346545
• DA
  Deutscher Akademischer Austauschdienst

  Award: award301004
• NO
  NIH Office of the Director

  Awards: award301003, award301024, R00DC013805-02, T32NS041234, R01NS092823, award346648, R01NS076054, award346647, award346646, F32NS101778