Abnormal thiamine-dependent processes in Alzheimer's Disease. Lessons from diabetes

Gibson, Gary E.; Hirsch, Joseph; Cirio, Rosanna; Jordan, Barry; Fonzetti, Pasquale; Elder, Jessica

doi:10.1016/j.mcn.2012.09.001

Cited by 75 publications

(57 citation statements)

References 98 publications

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“…Thus, TD may change CaMMK activity by altering intracellular Ca 2+ concentration and subsequently alter AMPK activity. Second, TD is known to disrupt glucose metabolism (Jhala and Hazell, 2011, Gibson et al, 2013); the disturbance in glucose metabolism is known to alter AMPK activity. Third, TD may modulate leptin signaling, such as increasing the expression of leptin and/or its receptor or stimulating leptin-mediated intracellular signaling in the hypothalamus.…”

Section: Discussionmentioning

confidence: 99%

Thiamine deficiency induces anorexia by inhibiting hypothalamic AMPK

Liu¹,

Alimov²,

Wang³

et al. 2014

Neuroscience

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Obesity and eating disorders are prevailing health concerns worldwide. It is important to understand the regulation of food intake and energy metabolism. Thiamine (vitamin B1) is an essential nutrient. Thiamine deficiency (TD) can cause a number of disorders in humans, such as Beriberi and Wernicke-Korsakoff syndrome. We demonstrated here that TD caused anorexia in C57BL/6 mice. After feeding a TD diet for 16 days, the mice displayed a significant decrease in food intake and an increase in resting energy expenditure (REE), which resulted in a severe weight loss. At the 22nd day, the food intake was reduced by 69% and 74% for male and female mice, respectively in TD group. The REE increased by 9 folds in TD group. The loss of body weight (17–24%) was similar between male and female animals and mainly resulted from the reduction of fat mass (49% decrease). Re-supplementation of thiamine (benfotiamine) restored animal's appetite, leading to a total recovery of body weight. The hypothalamic AMPK is a critical regulator of food intake. TD inhibited the phosphorylation of AMPK in the arcuate nucleus (ARN) and paraventricular nucleus (PVN) of the hypothalamus without affecting its expression. TD-induced inhibition of AMPK phosphorylation was reversed once thiamine was re-supplemented. In contrast, TD increased AMPK phosphorylation in the skeletal muscle and upregulated the uncoupling protein (UCP)-1 in brown adipose tissues which was consistent with increased basal energy expenditure. Re-administration of thiamine stabilized AMPK phosphorylation in the skeletal muscle as well as energy expenditure. Taken together, TD may induce anorexia by inhibiting hypothalamic AMPK activity. With a simultaneous increase in energy expenditure, TD caused an overall body weight loss. The results suggest that the status of thiamine levels in the body may affect food intake and body weight.

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Section: Discussionmentioning

confidence: 99%

Thiamine deficiency induces anorexia by inhibiting hypothalamic AMPK

Liu¹,

Alimov²,

Wang³

et al. 2014

Neuroscience

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“…Vitamin B 1 (thiamin) plays an important role as a cofactor in several biochemical pathways and especially high concentrations are found in heart, liver, kidney, brain and skeletal muscle. Inadequate thiamin has been observed in older subjects [294] and abnormal thiamin-dependent processes appear in AD [295]. Vitamin B 2 (riboflavin) is a cofactor in metabolic redox reactions, amino acid and lipid metabolism.…”

Section: The Role Of Trace Elements and Micronutrients In Agingmentioning

confidence: 99%

Happily (n)ever after: Aging in the context of oxidative stress, proteostasis loss and cellular senescence

et al. 2017

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Aging is a complex phenomenon and its impact is becoming more relevant due to the rising life expectancy and because aging itself is the basis for the development of age-related diseases such as cancer, neurodegenerative diseases and type 2 diabetes. Recent years of scientific research have brought up different theories that attempt to explain the aging process. So far, there is no single theory that fully explains all facets of aging. The damage accumulation theory is one of the most accepted theories due to the large body of evidence found over the years. Damage accumulation is thought to be driven, among others, by oxidative stress. This condition results in an excess attack of oxidants on biomolecules, which lead to damage accumulation over time and contribute to the functional involution of cells, tissues and organisms. If oxidative stress persists, cellular senescence is a likely outcome and an important hallmark of aging. Therefore, it becomes crucial to understand how senescent cells function and how they contribute to the aging process. This review will cover cellular senescence features related to the protein pool such as morphological and molecular hallmarks, how oxidative stress promotes protein modifications, how senescent cells cope with them by proteostasis mechanisms, including antioxidant enzymes and proteolytic systems. We will also highlight the nutritional status of senescent cells and aged organisms (including human clinical studies) by exploring trace elements and micronutrients and on their importance to develop strategies that might increase both, life and health span and postpone aging onset.

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“…It has been documented that the activities of these thiamine-dependent enzymes were also diminished in AD brains [53-55]. Moreover, the reductions in thiamine-dependent activity are associated with the severity of the dementia in AD patients [56]. In animal models, TD increased the accumulation of beta-amyloid, exacerbates plaque formation, promotes phosphorylation of tau and impairs memory, suggesting TD might play a role in the pathology of AD [57, 58].…”

Section: Td and Neurodegenerationmentioning

confidence: 99%

Thiamine Deficiency and Neurodegeneration: the Interplay Among Oxidative Stress, Endoplasmic Reticulum Stress, and Autophagy

2016

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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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Abnormal thiamine-dependent processes in Alzheimer's Disease. Lessons from diabetes

Cited by 75 publications

References 98 publications

Thiamine deficiency induces anorexia by inhibiting hypothalamic AMPK

Thiamine deficiency induces anorexia by inhibiting hypothalamic AMPK

Happily (n)ever after: Aging in the context of oxidative stress, proteostasis loss and cellular senescence

Thiamine Deficiency and Neurodegeneration: the Interplay Among Oxidative Stress, Endoplasmic Reticulum Stress, and Autophagy

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