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High doses of nicotinamide prevent oxidative mitochondrial dysfunction in a cellular model and improve motor deficit in a Drosophila model of Parkinson's disease
Author(s) -
Jia Haiqun,
Li Xin,
Gao Hongxiang,
Feng Zhihui,
Li Xuesen,
Zhao Lei,
Jia Xu,
Zhang Hongyu,
Liu Jiankang
Publication year - 2008
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.21650
Subject(s) - oxidative stress , neurodegeneration , nicotinamide , neuroprotection , mitochondrion , biochemistry , niacin , nad+ kinase , reactive oxygen species , nicotinamide adenine dinucleotide , sirt3 , oxidative phosphorylation , chemistry , biology , pharmacology , medicine , sirtuin , enzyme , disease
Nicotinamide, the principal form of niacin (vitamin B3), has been proposed to be neuroprotective in Parkinson's disease. However, the effects and mechanisms of nicotinamide on motor function in animals and on mitochondrial function in cellular systems have not been well studied. We hypothesized that niacin‐derived NAD(P)H as antioxidants and enzyme cofactors could inhibit oxidative damage and improve mitochondrial function and thus protect neurodegeneration and improve motor function. In the present study, the effects of nicotinamide on mitochondrial function and oxidative stress were studied in a 1‐methyl‐4‐phenylpyridinium (MPP + )–induced cellular model of Parkinson's disease, and the effects of improving motor dysfunction were studied in an α‐synuclein transgenic Drosophila Parkinson's model. Mitochondrial function was tested by measuring the activity of mitochondrial complex I and α‐ketoglutarate dehydrogenase, and oxidative damage was tested by measuring reactive oxygen species, DNA damage (8‐oxo‐7,8‐dihydro‐2′‐deoxyguanosine and Comet assay), and protein oxidation (protein carbonyls) levels. Nicotinamide at a relatively higher concentration, that is, 100‐fold of the level in the cell culture medium (101 mg/L), significantly protected SK‐N‐MC human neuroblastoma cells from an MPP + ‐induced decrease in cell viability, complex I and α‐ketoglutarate dehydrogenase activity, and an increase in oxidant generation, DNA damage, and protein oxidation. In the Drosophila model, nicotinamide at 15 and 30 mg/100 g diet significantly improved climbing ability. These results suggest that nutritional supplementation of nicotinamide at high doses decreases oxidative stress and improves mitochondrial and motor function in cellular and/or Drosophila models and may be an effective strategy for preventing and ameliorating Parkinson's disease. © 2008 Wiley‐Liss, Inc.