Thiamine Deficiency and Neurodegeneration: the Interplay Among Oxidative Stress, Endoplasmic Reticulum Stress, and Autophagy.
Thiamine (vitamin B1) is an essential nutrient and indispensable for normal growth and development of the organism due to its multilateral participation in key biochemical and physiological processes. Humans must obtain thiamine from their diet since it is synthesized only in bacteria, fungi, and plants. Thiamine deficiency (TD) can result from inadequate intake, increased requirement, excessive deletion, and chronic alcohol consumption. TD affects multiple organ systems, including the cardiovascular, muscular, gastrointestinal, and central and peripheral nervous systems. In the brain, TD causes a cascade of events including mild impairment of oxidative metabolism, neuroinflammation, and neurodegeneration, which are commonly observed in neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), and Huntington's disease (HD). Thiamine metabolites may serve as promising biomarkers for neurodegenerative diseases, and thiamine supplementations exhibit therapeutic potential for patients of some neurodegenerative diseases. Experimental TD has been used to model aging-related neurodegenerative diseases. However, to date, the cellular and molecular mechanisms underlying TD-induced neurodegeneration are not clear. Recent research evidence indicates that TD causes oxidative stress, endoplasmic reticulum (ER) stress, and autophagy in the brain, which are known to contribute to the pathogenesis of various neurodegenerative diseases. In this review, we discuss the role of oxidative stress, ER stress, and autophagy in TD-mediated neurodegeneration. We propose that it is the interplay of oxidative stress, ER stress, and autophagy that contributes to TD-mediated neurodegeneration.
Department of Medical Psychology, Shandong University School of Medicine, #44 Wenhua Xi Road, Jinan, Shandong, 250012, People's Republic of China.|Department of Pharmacology and Nutritional Sciences, College of Medicine, University of Kentucky, 132 Health Sciences Research Building, 1095 Veterans Drive, Lexington, KY, 40536, USA.
Dexiang
D
Liu
Department of Biochemistry, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
Zunji
Z
Ke
Department of Pharmacology and Nutritional Sciences, College of Medicine, University of Kentucky, 132 Health Sciences Research Building, 1095 Veterans Drive, Lexington, KY, 40536, USA. jialuo888@uky.edu.|Department of Biochemistry, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China. jialuo888@uky.edu.
Jia
J
Luo
D000437:Alcoholism / Q000378:metabolism; D000818:Animals; D001343:Autophagy / Q000502:physiology*; D059865:Endoplasmic Reticulum Stress / Q000502:physiology*; D006801:Humans; D019636:Neurodegenerative Diseases / Q000235:genetics / Q000378:metabolism*; D018384:Oxidative Stress / Q000502:physiology*; D013832:Thiamine Deficiency / Q000378:metabolism*
Alcoholism; Protein degradation; Reactive oxygen species; Unfolded protein response; Vitamin B1