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Nicotinamide riboside modulates the reactive species interactome, bioenergetic status and proteomic landscape in a brain-region-specific manner

ABSTRACT: Nicotinamine riboside (NR), a precursor of nicotinamide adenine dinucleotide (NAD+), has robust behavioral and cognitive benefits as well as effects alleviating neuroinflammation in AD mouse models. Gene expression studies hint benefitial induction of neuroprotective pathways for AD. However, the proteopathic nature of AD remains partially unaffected, as these mice fail to clear deposited beta-amyloid plaques. Such effects may be mediated by the reactive species interactome (RSI), key players at the metabolome level. In the current study, we employed in vitro and in vivo models of oxidative stress/aging/AD to profile the effects of NR on neuronal survival, RSI, and whole proteome landscape characterization of cortex and hippocampus. RSI analysis yielded a complex modulation upon NR treatment. Differential expression analysis yielded in subtle changes in protein expression. We constructed protein co-expression networks for each brain area and correlated them to NR treatment and every reactive species we measured. We observed brain-area specific effects of NR on co-expressed protein modules of oxidative phosphorylation, fatty acid oxidation, and neurotransmitter regulation pathways, which correlated with RSI components. The current study contributes to the understanding of modulation of the metabolome, specifically with NR, in AD may play disease-modifying roles.

ORGANISM(S): Mus Musculus

SUBMITTER: Amalia M Dolga

PROVIDER: PXD053897 | iProX | Thu Jul 11 00:00:00 BST 2024

REPOSITORIES: iProX

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Nicotinamide riboside modulates the reactive species interactome, bioenergetic status and proteomic landscape in a brain-region-specific manner.

Marmolejo-Garza Alejandro A Chatre Laurent L Croteau Deborah L DL Herron-Bedoya Alejandro A Luu Minh Danh Anh MDA Bernay Benoit B Pontin Julien J Bohr Vilhelm A VA Boddeke Erik E Dolga Amalia M AM

Neurobiology of disease 20240822

Nicotinamide riboside (NR), a precursor of nicotinamide adenine dinucleotide (NAD+), has robust cognitive benefits and alleviates neuroinflammation in Alzheimer's Disease (AD) mouse models without decreasing beta-amyloid plaque pathology. Such effects may be mediated by the reactive species interactome (RSI), at the metabolome level. In this study, we employed in vitro and in vivo models of oxidative stress, aging and AD to profile the effects of NR on neuronal survival, RSI, and the whole prote ...[more]

PMID: 39179121

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Nicotinamide riboside modulates the reactive species interactome, bioenergetic status and proteomic landscape in a brain-region-specific manner

Publications

Nicotinamide riboside modulates the reactive species interactome, bioenergetic status and proteomic landscape in a brain-region-specific manner.

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