Vitamin B12 impacts amyloid beta-induced proteotoxicity by regulating the methionine/S-adenosylmethionine cycle
Summary: 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...
Main Authors: | , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Elsevier
2021-09-01
|
Series: | Cell Reports |
Subjects: | |
Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124721012079 |
id |
doaj-2c1655510b96446d8592285be3180d09 |
---|---|
record_format |
Article |
spelling |
doaj-2c1655510b96446d8592285be3180d092021-10-01T04:57:28ZengElsevierCell Reports2211-12472021-09-013613109753Vitamin B12 impacts amyloid beta-induced proteotoxicity by regulating the methionine/S-adenosylmethionine cycleAndy B. Lam0Kirsten Kervin1Jessica E. Tanis2Department of Biological Sciences, University of Delaware, Newark, DE 19716, USADepartment of Biological Sciences, University of Delaware, Newark, DE 19716, USADepartment of Biological Sciences, University of Delaware, Newark, DE 19716, USA; Corresponding authorSummary: 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.http://www.sciencedirect.com/science/article/pii/S2211124721012079amyloid betavitamin B12dietmethionineS-adenosylmethioninecholine |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Andy B. Lam Kirsten Kervin Jessica E. Tanis |
spellingShingle |
Andy B. Lam Kirsten Kervin Jessica E. Tanis Vitamin B12 impacts amyloid beta-induced proteotoxicity by regulating the methionine/S-adenosylmethionine cycle Cell Reports amyloid beta vitamin B12 diet methionine S-adenosylmethionine choline |
author_facet |
Andy B. Lam Kirsten Kervin Jessica E. Tanis |
author_sort |
Andy B. Lam |
title |
Vitamin B12 impacts amyloid beta-induced proteotoxicity by regulating the methionine/S-adenosylmethionine cycle |
title_short |
Vitamin B12 impacts amyloid beta-induced proteotoxicity by regulating the methionine/S-adenosylmethionine cycle |
title_full |
Vitamin B12 impacts amyloid beta-induced proteotoxicity by regulating the methionine/S-adenosylmethionine cycle |
title_fullStr |
Vitamin B12 impacts amyloid beta-induced proteotoxicity by regulating the methionine/S-adenosylmethionine cycle |
title_full_unstemmed |
Vitamin B12 impacts amyloid beta-induced proteotoxicity by regulating the methionine/S-adenosylmethionine cycle |
title_sort |
vitamin b12 impacts amyloid beta-induced proteotoxicity by regulating the methionine/s-adenosylmethionine cycle |
publisher |
Elsevier |
series |
Cell Reports |
issn |
2211-1247 |
publishDate |
2021-09-01 |
description |
Summary: 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. |
topic |
amyloid beta vitamin B12 diet methionine S-adenosylmethionine choline |
url |
http://www.sciencedirect.com/science/article/pii/S2211124721012079 |
work_keys_str_mv |
AT andyblam vitaminb12impactsamyloidbetainducedproteotoxicitybyregulatingthemethioninesadenosylmethioninecycle AT kirstenkervin vitaminb12impactsamyloidbetainducedproteotoxicitybyregulatingthemethioninesadenosylmethioninecycle AT jessicaetanis vitaminb12impactsamyloidbetainducedproteotoxicitybyregulatingthemethioninesadenosylmethioninecycle |
_version_ |
1716862229842755584 |