'SNO'-Storms Compromise Protein Activity and Mitochondrial Metabolism in Neurodegenerative Disorders

Trends in Endocrinology and Metabolism : TEM
Tomohiro Nakamura, Stuart A Lipton

Abstract

The prevalence of neurodegenerative diseases, including Alzheimer's disease (AD) and Parkinson's disease (PD), is currently a major public health concern due to the lack of efficient disease-modifying therapeutic options. Recent evidence suggests that mitochondrial dysfunction and nitrosative/oxidative stress are key common mediators of pathogenesis. In this review, we highlight molecular mechanisms linking NO-dependent post-translational modifications, such as cysteine S-nitrosylation and tyrosine nitration, to abnormal mitochondrial metabolism. We further discuss the hypothesis that pathological levels of NO compromise brain energy metabolism via aberrant S-nitrosylation of key enzymes in the tricarboxylic acid (TCA) cycle and oxidative phosphorylation, contributing to neurodegenerative conditions. A better understanding of these pathophysiological events may provide a potential pathway for designing novel therapeutics to ameliorate neurodegenerative disorders.

Citations

Oct 4, 2018·Current Protocols in Protein Science·Paschalis-Thomas Doulias, Neal S Gould
Feb 7, 2019·Journal of Inherited Metabolic Disease·Julien BaruteauJohannes Häberle
Jul 30, 2019·Clinical Psychopharmacology and Neuroscience : the Official Scientific Journal of the Korean College of Neuropsychopharmacology·Gessica SalaLucio Tremolizzo
Jan 15, 2020·Antioxidants & Redox Signaling·Costanza MontagnaGiuseppe Filomeni
Apr 3, 2020·Antioxidants·Valentina Di PietroAngela Maria Amorini
Feb 26, 2020·European Psychiatry : the Journal of the Association of European Psychiatrists·Gerwyn MorrisBasant K Puri
Sep 29, 2020·Neurochemical Research·Yadi ZhangYumiao Lang
Dec 13, 2018·Neural Regeneration Research·Julie-Myrtille Bourgognon, Joern R Steinert
Mar 27, 2019·Proceedings of the National Academy of Sciences of the United States of America·Urbain WeyemiSolomon H Snyder
Oct 6, 2020·The Biochemical Journal·Salvatore Rizza, Giuseppe Filomeni
Mar 29, 2020·Molecular Metabolism·Meike Wiese, Andrew J Bannister
Jul 22, 2021·Archives of Pharmacal Research·Eun-Joo ShinHyoung-Chun Kim

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