Vitamin B12 Inhibits Aβ Fibrillation and Disaggregates Preformed Fibrils in the Presence of Synthetic Neuronal Membranes

Andrade, Stéphanie; Loureiro, Joana A.; Pereira, Maria do Carmo

doi:10.1021/acschemneuro.1c00210

Cited by 13 publications

(8 citation statements)

References 60 publications

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“…It has been shown that vitamin B12 reduces amyloid pathology by different mechanisms. These include the decreased gene expression of BACE1 and PS1 [ 135 , 136 , 137 , 138 ], two important enzymes for the release of Aβ peptides out of APP [ 139 , 140 , 141 , 142 ]; decreased cholesterol de novo synthesis [ 143 ]; and the inhibition of Aβ fibrillization and aggregation [ 128 , 144 ]. The protective effect of vitamin B12 in respect to tau hyperphosphorylation and tau aggregation is reported to be caused by an elevation in the activity of the phospholipase A2 [ 145 ], an inhibition of kinases involved in tau phosphorylation e.g., GSK-3β [ 146 ], and by the direct binding of vitamin B12 to tau proteins [ 147 ].…”

Section: Discussionmentioning

confidence: 99%

Vitamin B12 Attenuates Changes in Phospholipid Levels Related to Oxidative Stress in SH-SY5Y Cells

Theiss

Griebsch

Lauer

et al. 2022

Cells

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Oxidative stress is closely linked to Alzheimer’s disease (AD), and is detected peripherally as well as in AD-vulnerable brain regions. Oxidative stress results from an imbalance between the generation and degradation of reactive oxidative species (ROS), leading to the oxidation of proteins, nucleic acids, and lipids. Extensive lipid changes have been found in post mortem AD brain tissue; these changes include the levels of total phospholipids, sphingomyelin, and ceramide, as well as plasmalogens, which are highly susceptible to oxidation because of their vinyl ether bond at the sn-1 position of the glycerol-backbone. Several lines of evidence indicate that a deficiency in the neurotropic vitamin B12 is linked with AD. In the present study, treatment of the neuroblastoma cell line SH-SY5Y with vitamin B12 resulted in elevated levels of phosphatidylcholine, phosphatidylethanolamine, sphingomyelin, and plasmalogens. Vitamin B12 also protected plasmalogens from hydrogen peroxide (H2O2)-induced oxidative stress due to an elevated expression of the ROS-degrading enzymes superoxide-dismutase (SOD) and catalase (CAT). Furthermore, vitamin B12 elevates plasmalogen synthesis by increasing the expression of alkylglycerone phosphate synthase (AGPS) and choline phosphotransferase 1 (CHPT1) in SH-SY5Y cells exposed to H2O2-induced oxidative stress.

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Section: Discussionmentioning

confidence: 99%

Vitamin B12 Attenuates Changes in Phospholipid Levels Related to Oxidative Stress in SH-SY5Y Cells

Theiss

Griebsch

Lauer

et al. 2022

Cells

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“…In a recent study (2021), the inhibitory effect of vitamin B12 on Aβ fibrillation could be shown by the use of artificial neuronal membranes mimicked by liposomes as Aβ generation is strongly influenced by the lipid environment of cellular membranes. To mimic neuronal cell membranes, lipid components at comparable ratios were chosen to compose the lipid vesicle: phosphatidylcholines (1,2-dimyristol-sn-glycero-3-phosphocholine), cholesterol, sphingomyelin and phosphatidylserine (L-α-phosphatidylserine) [ 153 ]. Performing a ThT fluorescent assay in the presence of Aβ1–42 and presence or absence of vitamin B12 the authors found that vitamin B12 slows down the transition from Aβ oligomers to mature fibrils and significantly reduced the content of fibrils in aqueous solution without the synthetic neuronal membranes.…”

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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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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“…Cationic liposomes were also produced by the thin-film hydration method followed by extrusion [38]. DOTAP and CHOL (molar ratio 85:15) were dissolved in chloroform, and a thin lipid film was obtained after the evaporation of the organic solvent under a nitrogen stream.…”

Section: Preparation Of Liposomesmentioning

confidence: 99%

Multi-Dose Intravenous Administration of Neutral and Cationic Liposomes in Mice: An Extensive Toxicity Study

et al. 2022

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Liposomes are widely used as delivery systems for therapeutic purposes. However, the toxicity associated with the multi-dose administration of these nanoparticles is not fully elucidated. Here, we evaluated the toxicity of the prolonged administration of liposomes composed of neutral or cationic phospholipids often used in drug and gene delivery. For that purpose, adult wild-type mice (C57Bl6) were randomly distributed into three groups receiving either vehicle (PBS), neutral, or cationic liposomes and subjected to repeated intravenous injections for a total of 10 doses administered over 3 weeks. Several parameters, including mortality, body weight, and glucose levels, were monitored throughout the trial. While these variables did not change in the group treated with neutral liposomes, the group treated with the positively charged liposomes displayed a mortality rate of 45% after 10 doses of administration. Additional urinalysis, blood tests, and behavioral assays to evaluate impairments of motor functions or lesions in major organs were also performed. The cationic group showed less forelimb peak force than the control group, alterations at the hematological level, and inflammatory components, unlike the neutral group. Overall, the results demonstrate that cationic liposomes are toxic for multi-dose administration, while the neutral liposomes did not induce changes associated with toxicity. Therefore, our results support the use of the well-known neutral liposomes as safe drug shuttles, even when repetitive administrations are needed.

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Vitamin B12 Inhibits Aβ Fibrillation and Disaggregates Preformed Fibrils in the Presence of Synthetic Neuronal Membranes

Cited by 13 publications

References 60 publications

Vitamin B12 Attenuates Changes in Phospholipid Levels Related to Oxidative Stress in SH-SY5Y Cells

Vitamin B12 Attenuates Changes in Phospholipid Levels Related to Oxidative Stress in SH-SY5Y Cells

Mechanistic Link between Vitamin B12 and Alzheimer’s Disease

Multi-Dose Intravenous Administration of Neutral and Cationic Liposomes in Mice: An Extensive Toxicity Study

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