Cell death in Parkinson's disease

J Neurol. 2002 Sep:249 Suppl 2:II6-10. doi: 10.1007/s00415-002-1202-6.

Abstract

The cause of neuronal cell death in Parkinson's disease is still an enigma. However, recent results obtained by analyses of postmortem brain suggest that a mitochondria-dependent apoptotic signal was activated. The involvement of dopamine-derived endogenous neurotoxin in the pathogenesis of PD was also indicated. N-Methyl( R)salsolinol was proved to be selectively toxic to dopamine neurons and its level increased in parkinsonian CSF. The enzyme which determines the level of N-methyl( R)salsolinol, ( R)salsolinol N-methyltransferase, was found increased in the lymphocytes prepared from PD patients. The mechanism of dopamine cell death by N-methyl( R)salsolinol was studied in vitro. N-Methyl( R)salsolinol induced apoptosis in human dopaminergic neuroblastoma cells. It was suggested that in the mitochondria there is a molecule which interacts with N-methyl( R)salsolinol and initiates an apoptotic signal.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis* / drug effects
  • Brain / drug effects
  • Brain / physiopathology
  • Cell Count
  • Disease Models, Animal
  • Humans
  • Isoquinolines / metabolism
  • Isoquinolines / toxicity
  • Male
  • Mitochondria / metabolism
  • Neurons / drug effects
  • Neurons / metabolism
  • Neurons / pathology
  • Neurotoxins / metabolism
  • Neurotoxins / toxicity*
  • Oxidative Stress
  • Parkinsonian Disorders / etiology*
  • Parkinsonian Disorders / pathology*
  • Parkinsonian Disorders / physiopathology
  • Rats
  • Rats, Wistar
  • Salsoline Alkaloids / metabolism
  • Salsoline Alkaloids / toxicity*
  • Signal Transduction / drug effects
  • Tetrahydroisoquinolines*
  • Tumor Cells, Cultured

Substances

  • Isoquinolines
  • Neurotoxins
  • Salsoline Alkaloids
  • Tetrahydroisoquinolines
  • salsoline