NAD⁺-boosting agent nicotinamide mononucleotide potently improves mitochondria stress response in Alzheimer's disease via ATF4-dependent mitochondrial UPR.

ABSTRACT: Extensive studies indicate that mitochondria dysfunction is pivotal for Alzheimer's disease (AD) pathogenesis; while cumulative evidence suggests that increased mitochondrial stress response (MSR) may mitigate neurodegeneration in AD, explorations to develop a MSR-targeted therapeutic strategy against AD are scarce. We combined cell biology, molecular biology, and pharmacological approaches to unravel a novel molecular pathway by which NAD⁺-boosting agent nicotinamide mononucleotide (NMN) regulates MSR in AD models. Here, we report dyshomeostasis plasma UPR^mt-mitophagy-mediated MSR profiles in AD patient samples. NMN restores NAD⁺ metabolic profiles and improves MSR through the ATF4-dependent UPR^mt pathway in AD-related cross-species models. At t

SUBMITTER: Xiong X 

PROVIDER: S-EPMC11470026 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature