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Increased brain NAD prevents neuronal apoptosis in vivo
S K Mukherjee1, L K Klaidman, R Yasharel
1School of Pharmacy, Department of Molecular Pharmacology and Toxicology, University of Southern California, Los Angeles 90033, USA.
Abstract:
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.
Insights
1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induces apoptosis and DNA fragmentation in dopaminergic neurons. Nicotinamide, a NAD precursor, blocks MPTP-induced apoptosis and may aid in treating neurodegeneration.
Area of Science:
- Neuroscience
- Cell Biology
- Toxicology
Background:
- Apoptosis, a programmed cell death, is linked to neurodegenerative diseases.
- 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a neurotoxin that selectively targets dopaminergic neurons in the substantia nigra.
- MPTP is known to generate reactive oxygen species.
Purpose of the Study:
- To investigate the induction of apoptosis and DNA fragmentation in vivo by MPTP.
- To evaluate the neuroprotective effects of nicotinamide against MPTP toxicity.
Main Methods:
- In vivo administration of MPTP to induce neurotoxicity.
- Assessment of apoptosis and DNA fragmentation in affected neuronal populations.
- Administration of nicotinamide to assess its protective role.
Main Results:
- MPTP exposure led to significant apoptosis and DNA fragmentation in dopaminergic neurons.
- Nicotinamide administration effectively blocked MPTP-induced apoptosis.
- Nicotinamide demonstrated radical-quenching properties, potentially via xanthine oxidase inhibition.
Conclusions:
- MPTP triggers apoptosis and DNA damage in dopaminergic neurons, contributing to neurodegeneration.
- Nicotinamide exhibits neuroprotective effects against MPTP toxicity by inhibiting apoptosis.
- Nicotinamide's ability to quench radicals suggests its potential therapeutic value in neurodegenerative conditions.