Increased brain NAD prevents neuronal apoptosis in vivo.
Apoptosis is a characteristic form of cell death which has been implicated in neurodegeneration. In this study we document the induction of apoptosis and DNA fragmentation in vivo by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a neurotoxin. MPTP selectively damages dopaminergic neurons in the substantia nigra of the midbrain. It is a potent inducer of oxygen radicals. Nicotinamide, a precursor of NAD, is able to block the apoptosis induced by MPTP. Nicotinamide also quenches some of the radicals formed by xanthine oxidase. Nicotinamide may be of interest in the treatment of neurodegeneration.
Mukherjee
S K
SK
School of Pharmacy, Department of Molecular Pharmacology and Toxicology, University of Southern California, Los Angeles 90033, USA.
Klaidman
L K
LK
Yasharel
R
R
Adams
J D
JD
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001921:Brain / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D053938:DNA Fragmentation / Q000187:drug effects; D004578:Electron Spin Resonance Spectroscopy; D005609:Free Radicals / Q000378:metabolism; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D009243:NAD / Q000378:metabolism / Q000502:physiology*; D009474:Neurons / Q000187:drug effects*; D009536:Niacinamide / Q000494:pharmacology; D013378:Substantia Nigra / Q000166:cytology / Q000201:enzymology
D005609:Free Radicals; D009243:NAD; D009536:Niacinamide; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine