Cell death in Parkinson's disease.

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.

• Authors: Wakako Maruyama, Makoto Naoi
• Journal: Journal of neurology (J Neurol) Vol. 249 Suppl 2 Pg. II6-10 (Sep 2002) ISSN: 0340-5354 [Print] Germany
• PMID: 12375057 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Isoquinolines
• Neurotoxins
• Salsoline Alkaloids
• Tetrahydroisoquinolines
• salsoline

Topics

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