Possible role of 1-methylnicotinamide in the pathogenesis of Parkinson's disease

Experimental and Toxicologic Pathology : Official Journal of the Gesellschaft Für Toxikologische Pathologie
Tetsuhito FukushimaMasaki Moriyama

Abstract

This study tested the hypothesis, that nicotinamide N-methyltransferase (NAMT) activity in the brain could convert nicotinamide to 1-methylnicotinamide (MNA) and by that means damage the nigro-neostriatal dopaminergic neurons. The NAMT activities of rat brain and liver were assayed with gas chromatographic-mass spectrometric analysis in a selected ion monitoring system. They amounted to 0.30 nmol/mg x h and 0.51 nmol/mg x h, respectively. The MNA injection in rat substantia nigra pars compacta significantly decreased dopamine content in the striatum. NADH oxidation and lipid peroxidation by MNA via rat brain submitochondrial particles (SMP) under the condition of pH ranging from pH 6.0 to 10.0 were verified. The pH optimum for the NADH oxidation was 9.0. The pH optimum for the peroxidation of the lipid composing SMP by MNA was also 9.0. The lipid peroxidation in this assay was suppressed by superoxide dismutase. The superoxide anion formed by MNA via mitochondria might be involved in the etiology of Parkinson's disease.

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Citations

Jul 1, 2005·Environmental Health and Preventive Medicine·Akiko SugawaraTetsuhito Fukushima
Jan 18, 2012·Environmental Health and Preventive Medicine·Yayoi MoriTetsuhito Fukushima
Jan 1, 2005·Environmental Health and Preventive Medicine·Tetsuhito Fukushima
Feb 25, 2005·QJM : Monthly Journal of the Association of Physicians·A C WilliamsD B Ramsden
Feb 24, 2016·Scientific Reports·Pamela FarshimAlexis Bailey
Sep 27, 2005·Parkinsonism & Related Disorders·Adrian Williams, David Ramsden
Jan 11, 2005·Journal of Clinical Neuroscience : Official Journal of the Neurosurgical Society of Australasia·Adrian C Williams, David B Ramsden
Oct 17, 2017·Endocrine Research·Bianca RudolphiDaniel Kraus
May 6, 2020·Biomolecules·Eun Seong Hwang, Seon Beom Song
Mar 25, 2009·Pharmacological Reports : PR·Cezary WatałaStefan Chłopicki
Nov 23, 2019·International Journal of Molecular Sciences·Rita Moretti, Costanza Peinkhofer

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