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Therapeutic effect of nicotinamide mononucleotide on Alzheimer's disease through activating autophagy and anti-oxidative stress.
- Source :
-
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie [Biomed Pharmacother] 2024 Sep; Vol. 178, pp. 117199. Date of Electronic Publication: 2024 Jul 24. - Publication Year :
- 2024
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Abstract
- Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the deposition of β-amyloid (Aβ) plaques and neurofibrillary tangles composed of tau protein in the brain. These neuropathological hallmarks contribute to cognitive impairment by inducing neuronal loss in the cerebral cortex and hippocampus. Unfortunately, current therapeutic approaches only target symptomatic relief and do not impede disease progression. Nicotinamide mononucleotide (NMN), a precursor of nicotinamide adenine dinucleotide (NAD <superscript>+</superscript> ), has emerged as a promising candidate for the treatment of age-related neurodegenerative disorders. NMN supplementation could restore NAD <superscript>+</superscript> levels, thereby alleviating neuronal damage and slowing the progression of AD and other aging-associated diseases. AD is closely associated with autophagic impairment and oxidative stress. Our in vivo experiments demonstrated that NMN could ameliorate pathological and behavioral impairments in AD mice. Specifically, NMN enhanced autophagy and promoted p-tau clearance. Meanwhile, NMN could activate the Nrf2/Keap1/NQO1 pathway, thereby reducing the oxidative stress. Immunofluorescence results demonstrated that NMN could alleviate neuronal damage in AD mice. Furthermore, in vitro results showed that the p-tau clearance and antioxidant stress effects of NMN were suppressed by autophagy inhibitor, chloroquine (CQ) or bafilomycin A1 (BafA1), in Aβ-induced PC12 cells. Lastly, when Nrf2 was knocked down, the antioxidant stress, autophagy enhancement, and p-tau clearance effects of NMN were all inhibited. In conclusion, our research indicates that NMN exerts therapeutic effect against AD by activating autophagy and the Nrf2/Keap1/NQO1 pathway through a mutual regulating mechanism of autophagy and antioxidative stress. These findings highlight the promising potential of NMN for the treatment of AD.<br />Competing Interests: Declaration of Competing Interest We declare that we have no financial and personal relationships with other people organizations that can inappropriately influence our work, there is no professional other personal interest of any nature or kind in any product, service and/or company that could be construed as influencing the position presented in, or the review of, the manuscript entitled.<br /> (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)
- Subjects :
- Animals
Mice
Antioxidants pharmacology
Antioxidants therapeutic use
tau Proteins metabolism
Kelch-Like ECH-Associated Protein 1 metabolism
Mice, Transgenic
Male
Disease Models, Animal
NAD(P)H Dehydrogenase (Quinone) metabolism
PC12 Cells
Rats
Amyloid beta-Peptides metabolism
Mice, Inbred C57BL
Signal Transduction drug effects
Oxidative Stress drug effects
Alzheimer Disease drug therapy
Alzheimer Disease metabolism
Alzheimer Disease pathology
Autophagy drug effects
Nicotinamide Mononucleotide pharmacology
Nicotinamide Mononucleotide therapeutic use
NF-E2-Related Factor 2 metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1950-6007
- Volume :
- 178
- Database :
- MEDLINE
- Journal :
- Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie
- Publication Type :
- Academic Journal
- Accession number :
- 39053426
- Full Text :
- https://doi.org/10.1016/j.biopha.2024.117199