Vitamin B12 impacts amyloid beta-induced proteotoxicity by regulating the methionine/S-adenosylmethionine cycle

Lam, Andy B.; Kervin, Kirsten; Tanis, Jessica E.

doi:10.1016/j.celrep.2021.109753

Cited by 32 publications

(21 citation statements)

References 73 publications

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“…Beside the studies revealing positive effects of vitamin B12 supplementation in transgenic mice and rats of different age, recent studies in 2021 used the roundworm Caenorhabditis elegans as an animal model to investigate the effects of vitamin B12 on amyloid-β toxicity [ 147 , 148 ]. Transgenic expression of human Aβ42 peptides in C. elegans body wall muscles causes AD-like pathological characteristics such as reduced ATP levels, defects in mitochondrial morphology, increased oxidative stress and a robust time-dependent paralysis [ 149 , 150 , 151 ].…”

Section: Vitamin B12 Cell Culture and Animal Studies Related To The Molecular Mechanisms Of Ad And Ad Pathologymentioning

confidence: 99%

“…Transgenic C. elegans worms lacking vitamin B12 supplementation exhibited paralysis faster and more severely than worms that received vitamin B12 supplementation [ 147 ]. In-line vitamin B12 supplementation delayed Aβ-induced paralysis [ 148 ]. Along with delayed paralysis, Aβ-expressing C. elegans receiving a vitamin B12-containing diet showed a higher ATP level, decreased mitochondrial fragmentation and reduced oxidative species (ROS) than those without vitamin B12.…”

Section: Vitamin B12 Cell Culture and Animal Studies Related To The Molecular Mechanisms Of Ad And Ad Pathologymentioning

confidence: 99%

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Mechanistic Link between Vitamin B12 and Alzheimer’s Disease

Lauer

Grimm

Apel³

et al. 2022

Biomolecules

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Alzheimer’s disease (AD) is the most common form of dementia in the elderly population, affecting over 55 million people worldwide. Histopathological hallmarks of this multifactorial disease are an increased plaque burden and tangles in the brains of affected individuals. Several lines of evidence indicate that B12 hypovitaminosis is linked to AD. In this review, the biochemical pathways involved in AD that are affected by vitamin B12, focusing on APP processing, Aβ fibrillization, Aβ-induced oxidative damage as well as tau hyperphosphorylation and tau aggregation, are summarized. Besides the mechanistic link, an overview of clinical studies utilizing vitamin B supplementation are given, and a potential link between diseases and medication resulting in a reduced vitamin B12 level and AD are discussed. Besides the disease-mediated B12 hypovitaminosis, the reduction in vitamin B12 levels caused by an increasing change in dietary preferences has been gaining in relevance. In particular, vegetarian and vegan diets are associated with vitamin B12 deficiency, and therefore might have potential implications for AD. In conclusion, our review emphasizes the important role of vitamin B12 in AD, which is particularly important, as even in industrialized countries a large proportion of the population might not be sufficiently supplied with vitamin B12.

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Section: Vitamin B12 Cell Culture and Animal Studies Related To The Molecular Mechanisms Of Ad And Ad Pathologymentioning

confidence: 99%

Section: Vitamin B12 Cell Culture and Animal Studies Related To The Molecular Mechanisms Of Ad And Ad Pathologymentioning

confidence: 99%

Mechanistic Link between Vitamin B12 and Alzheimer’s Disease

Lauer

Grimm

Apel³

et al. 2022

Biomolecules

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“…In accordance, patients deficient in CBS, a core enzyme for the transsulfuration of Hcy to cystathionine, display increased DNA damage due to Hcy accumulation [ 216 ]. Recent studies highlight the importance of adequate vitamin B12 intake in alleviating ROS-mediated oxidative damage and Aβ-induced paralysis in C. elegans AD models [ 217 , 218 ]. Importantly, they showed that this protective effect of B12 relies on its ability to promote Hcy remethylation by acting as a cofactor for MTR in the methionine cycle [ 218 ].…”

Section: One-carbon Metabolism and Neurodegenerationmentioning

confidence: 99%

“…Recent studies highlight the importance of adequate vitamin B12 intake in alleviating ROS-mediated oxidative damage and Aβ-induced paralysis in C. elegans AD models [ 217 , 218 ]. Importantly, they showed that this protective effect of B12 relies on its ability to promote Hcy remethylation by acting as a cofactor for MTR in the methionine cycle [ 218 ]. Interestingly, betaine supplementation in C. elegans is also protective against Aβ-induced toxicity, although this mechanism does not involve Hcy remethylation, but rather depends on the CBS-mediated transsulfuration pathway [ 219 ].…”

Section: One-carbon Metabolism and Neurodegenerationmentioning

confidence: 99%

One-Carbon Metabolism: Pulling the Strings behind Aging and Neurodegeneration

Lionaki

Ploumi

Tavernarakis

2022

Cells

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One-carbon metabolism (OCM) is a network of biochemical reactions delivering one-carbon units to various biosynthetic pathways. The folate cycle and methionine cycle are the two key modules of this network that regulate purine and thymidine synthesis, amino acid homeostasis, and epigenetic mechanisms. Intersection with the transsulfuration pathway supports glutathione production and regulation of the cellular redox state. Dietary intake of micronutrients, such as folates and amino acids, directly contributes to OCM, thereby adapting the cellular metabolic state to environmental inputs. The contribution of OCM to cellular proliferation during development and in adult proliferative tissues is well established. Nevertheless, accumulating evidence reveals the pivotal role of OCM in cellular homeostasis of non-proliferative tissues and in coordination of signaling cascades that regulate energy homeostasis and longevity. In this review, we summarize the current knowledge on OCM and related pathways and discuss how this metabolic network may impact longevity and neurodegeneration across species.

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“…11 In an Alzheimer's disease study, Vitamin B12 (acting on the methionine/ SAM cycle) exerted a protective effect by reducing mitochondrial fragmentation and oxidative stress. 12 In addition, a study of the Nrf2 gene in the frontal cortex of individuals with autism spectrum disorder found that Nrf2 gene expression was positively correlated with the abundances of MeCbl, methionine, and SAM. 13 In vitro experiments have shown that vitamin B12 can act as an effective antioxidant to inhibit the production of intracellular peroxides and prevent the apoptosis caused by H 2 O 2 .…”

Section: Introductionmentioning

confidence: 99%

Methylcobalamin Protects Melanocytes from H2O2-Induced Oxidative Stress by Activating the Nrf2/HO-1 Pathway

An¹,

Liu²,

Dong³

et al. 2021

DDDT

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Purpose: Oxidative stress is considered a major determinant in the pathogenesis of vitiligo. Methylcobalamin (MeCbl) is an activated form of vitamin B12 that regulates inflammatory factors, counters oxidative stress, and reduces apoptosis in many disease models. However, the specific mechanism of MeCbl repigmentation against vitiligo is unknown. In this study, we explored the effect of MeCbl on melanocytes following hydrogen peroxide (H 2 O 2 )induced oxidative stress. Methods: We established an oxidative stress model using the immortalized human normal melanocyte cell line PIG1. We used a Cell Counting Kit-8 (CCK-8) to detect drug cytotoxicity, and we measured the melanin content of cells using the NaOH method. Intracellular oxidative damage was assessed by flow cytometry and antioxidant enzyme detection kits. In addition, we assessed the presence of apoptosis by flow cytometry and Western blots. We explored the underlying mechanisms of MeCbl during oxidative stress in melanocytes by analyzing the results of experiments based on real-time quantitative polymerase chain reaction (RT-qPCR), Western blotting, and laser scanning confocal immunofluorescence microscopy. Finally, we repeated the experiments after applying an inhibitor to block the Nrf2 pathway. Results: We found that MeCbl treatment enhanced cell viability, increased melanin content, reduced intracellular reactive oxygen species (ROS) accumulation, increased the activities of antioxidant enzyme superoxide dismutase (SOD) and catalase (CAT), reduced melanocyte apoptosis, and up-regulated the expression of the Nrf2/HO-1 pathway. Moreover, the protective effects of MeCbl were significantly weakened after inhibiting the Nrf2/HO-1 pathway. Conclusion:Our results indicate that MeCbl attenuated the H 2 O 2 -induced oxidative stress in melanocytes by activating the Nrf2/HO-1 pathway, this suggests that MeCbl may be an effective treatment against vitiligo.

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Vitamin B12 impacts amyloid beta-induced proteotoxicity by regulating the methionine/S-adenosylmethionine cycle

Cited by 32 publications

References 73 publications

Mechanistic Link between Vitamin B12 and Alzheimer’s Disease

Mechanistic Link between Vitamin B12 and Alzheimer’s Disease

One-Carbon Metabolism: Pulling the Strings behind Aging and Neurodegeneration

Methylcobalamin Protects Melanocytes from H2O2-Induced Oxidative Stress by Activating the Nrf2/HO-1 Pathway

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