Abstract
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.
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Abbreviations
- AD:
-
Alzheimer’s disease
- ALS:
-
Amyotrophic lateral sclerosis
- ATF6:
-
Activating transcription factor-6
- ER:
-
Endoplasmic reticulum
- HD:
-
Huntington’s disease
- HNE:
-
4-Hydroxynonenal
- IRE1:
-
Inositol requiring protein-1
- KGDHC:
-
α-Ketoglutarate dehydrogenase complex
- PD:
-
Parkinson’s disease
- PDHC:
-
Pyruvate dehydrogenase complex
- PERK:
-
Protein kinase RNA-like ER kinase
- PRD:
-
Prion-related diseases
- ROS:
-
Reactive oxygen species
- TD:
-
Thiamine deficiency
- TPP:
-
Thiamine pyrophosphate
- UPR:
-
Unfolded protein response
- WKS:
-
Wernicke-Korsakoff syndrome
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Acknowledgments
We thank Jacqueline Frank for reading this manuscript. This work was supported by grants from the National Institutes of Health (NIH) (AA017226 and AA015407). It is also supported in part by the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development (Biomedical Laboratory Research and Development BX001721).
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Liu, D., Ke, Z. & Luo, J. Thiamine Deficiency and Neurodegeneration: the Interplay Among Oxidative Stress, Endoplasmic Reticulum Stress, and Autophagy. Mol Neurobiol 54, 5440–5448 (2017). https://doi.org/10.1007/s12035-016-0079-9
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DOI: https://doi.org/10.1007/s12035-016-0079-9