N-methyl-(R)salsolinol as a dopaminergic neurotoxin: from an animal model to an early marker of Parkinson's disease.
J Neural Transm Suppl
; 50: 89-105, 1997.
Article
en En
| MEDLINE
| ID: mdl-9120428
ABSTRACT
A dopamine-derived 1(R), 2(N)-dimethyl-6,7-dihydroxy-1,2,3,4-tetrahydrosioquinoline [N-methyl-(R)salsolinol] was found to occur enantioselectively in human brain. This isoquinoline induced parkinsonism in rat after injection in the striatum, and the behavioral, biochemical and pathological changes were very similar to those in Parkinson's disease. N-Methyl-(R)salsolinol depleted dopamine neurons in the rat substantia nigra without necrotic tissue reaction, which may be due to the apoptotic death process, as proved by its induction of DNA damage in dopaminergic neuroblastoma SH-SY5Y cells. N-Methyl-(R)salsolinol was found to increase significantly in the cerebrospinal fluid of parkinsonian patients. All these results suggest that N-methyl-(R)salsolinol may be an endogenous neurotoxin to cause Parkinson's disease and the enzymes involved in its biosynthesis and catabolism may be endogenous factors in the pathogenesis of this disease.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Enfermedad de Parkinson
/
Enfermedad de Parkinson Secundaria
/
Alcaloides de Salsolina
/
Encéfalo
/
Tetrahidroisoquinolinas
/
Neurotoxinas
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Humans
/
Male
Idioma:
En
Revista:
J Neural Transm Suppl
Año:
1997
Tipo del documento:
Article
País de afiliación:
Japón