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

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Author(s)Lam, Andy B.
Author(s)Kervin, Kirsten
Author(s)Tanis, Jessica E.
Date Accessioned2022-01-12T20:06:09Z
Date Available2022-01-12T20:06:09Z
Publication Date2021-09-28
DescriptionThis article was originally published in Cell Reports. The version of record is available at: https://doi.org/10.1016/j.celrep.2021.109753en_US
AbstractAlzheimer’s disease (AD) is a devastating neurodegenerative disorder with no effective treatment. Diet, as a modifiable risk factor for AD, could potentially be targeted to slow disease onset and progression. However, complexity of the human diet and indirect effects of the microbiome make it challenging to identify protective nutrients. Multiple factors contribute to AD pathogenesis, including amyloid beta (Aβ) deposition, energy crisis, and oxidative stress. Here, we use Caenorhabditis elegans to define the impact of diet on Aβ proteotoxicity. We discover that dietary vitamin B12 alleviates mitochondrial fragmentation, bioenergetic defects, and oxidative stress, delaying Aβ-induced paralysis without affecting Aβ accumulation. Vitamin B12 has this protective effect by acting as a cofactor for methionine synthase, impacting the methionine/S-adenosylmethionine (SAMe) cycle. Vitamin B12 supplementation of B12-deficient adult Aβ animals is beneficial, demonstrating potential for vitamin B12 as a therapy to target pathogenic features of AD triggered by proteotoxic stress.en_US
SponsorWe thank Jeffrey Caplan from the University of Delaware BioImaging Center for writing the script to measure mitochondrial length. Nematode strains were provided by the Caenorhabditis Genetics Center, which is supported by the NIH-ORIP ( P40 OD010440 ). Microscopy access was supported by grants from the NIH-NIGMS ( P20 GM103446 ), NSF ( IIA-1301765 ), and the State of Delaware . This work was supported by a University of Delaware Graduate Scholars award (to A.B.L.), NIH-NIGMS INBRE Pilot Project grant P20 GM103446 , NIGMS-NIH Alzheimer’s Supplement P20 GM103446-21S1 , and University of Delaware Research Foundation Award 18A00929 (to J.E.T.).en_US
CitationLam et al., 2021, Cell Reports 36, 109753 September 28, 2021. Copyright 2021 The Authors. https://doi.org/10.1016/j.celrep.2021.109753en_US
ISSN2211-1247
URLhttps://udspace.udel.edu/handle/19716/29968
Languageen_USen_US
PublisherCell Reportsen_US
Keywordsamyloid betaen_US
Keywordsvitamin B12en_US
Keywordsdieten_US
Keywordsmethionineen_US
KeywordsS-adenosylmethionineen_US
Keywordscholineen_US
KeywordsATPen_US
KeywordsAlzheimer’s diseaseen_US
KeywordsC. elegansen_US
TitleVitamin B12 impacts amyloid beta-induced proteotoxicity by regulating the methionine/S-adenosylmethionine cycleen_US
TypeArticleen_US
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