Vitamin B12 impacts amyloid beta-induced proteotoxicity by regulating the methionine/S-adenosylmethionine cycle
Date
2021-09-28
Journal Title
Journal ISSN
Volume Title
Publisher
Cell Reports
Abstract
Alzheimer’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.
Description
This article was originally published in Cell Reports. The version of record is available at: https://doi.org/10.1016/j.celrep.2021.109753
Keywords
amyloid beta, vitamin B12, diet, methionine, S-adenosylmethionine, choline, ATP, Alzheimer’s disease, C. elegans
Citation
Lam et al., 2021, Cell Reports 36, 109753 September 28, 2021. Copyright 2021 The Authors. https://doi.org/10.1016/j.celrep.2021.109753