Cell death of dopamine neurons in aging
and Parkinson's disease

by
Naoi M, Maruyama W.
Department of Brain Sciences,
Institute of Applied Biochemistry,
Mitake, Gifu, Japan.
appbio@mbf.sphere.ne.jp
Mech Ageing Dev. 1999 Nov;111(2-3):175-88


ABSTRACT

Dopamine neurons in the substantia nigra of human brain are selectively vulnerable and the number decline by aging at 5-10% per decade. Enzymatic and non-enzymatic oxidation of dopamine generates reactive oxygen species, which induces apoptotic cell death in dopamine neurons. Parkinson's disease (PD) is also caused by selective cell death of dopamine neurons in this brain region. The pathogenesis of Parkinson's disease remains to be an enigma, but it was found that an endogenous MPTP-like neurotoxin, 1(R), 2(N)-dimethyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline [N-methyl(R)salsolinol, NM(R)Sal], may be one of the pathogenic agents of PD. NM(R)Sal increases in cerebrospinal fluid from untreated parkinsonian patients, and two enzymes, a (R)salsolinol synthase and a neutral N-methyltransferase, synthesize this neurotoxin in the nigro-striatum. The activity of a neutral N-methyltransferase is significantly higher in lymphocytes from parkinsonian patients than in control. The mechanism of cell death by this toxin was proved to be by the induction of apoptosis, by use of dopaminergic SH-SY5Y cells. The apoptosis was suppressed by anti-oxidants, suggesting that the generation of reactive oxygen species may initiate cellular death process. These results indicate that in aging and PD oxidative stress induces degeneration of dopamine neurons, and the antioxidant therapy may delay the decline of dopamine neurons in the brain.


MAOIs
Dopamine
Rasagiline: structure
MAO-b inhibitors/PD
Anti-apoptotic activity
Parkinson's disease: resources
Anti-Alzheimer/anti-Parkinson's drugs
Parkinson's disease and sleep disorders
Rasagiline/ anti-apoptotic bcl-2 gene family
Dual AChE and MAO inhibitors and Alzheimer's
Rasagiline v selegiline: neuronal survival effects
Rasagiline (Agilect) in early Parkinson's disease
Normal aging and nigral dopaminergic cell death


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