2. Academic Validation
  3. Therapeutic effect of nicotinamide mononucleotide on Alzheimer's disease through activating autophagy and anti-oxidative stress

Therapeutic effect of nicotinamide mononucleotide on Alzheimer's disease through activating autophagy and anti-oxidative stress

  • Biomed Pharmacother. 2024 Sep:178:117199. doi: 10.1016/j.biopha.2024.117199.
Rui-Yin Ma 1,  Li Li 2,  Hui Yang 3,  Bin Zou 1,  Rui-Xia Ma 1,  Yue Zhang 1,  Miao-Miao Wu 1,  Peng Chen 4,  Yao Yao 5,  Juan Li 6
Affiliations

Affiliations

  • 1 School of Pharmacy, Ningxia Medical University, Yinchuan 750004, China.
  • 2 Department of Pharmacy, The Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen 518000, China.
  • 3 Research Center of Medical Science and Technology, Ningxia Medical University, Yinchuan 750004, China.
  • 4 School of Clinical Medicine, Ningxia Medical University, Yinchuan 750004, China.
  • 5 School of Basic Medical Sciences, Ningxia Medical University, Yinchuan 750004, China. Electronic address: 20070007@nxmu.edu.cn.
  • 6 School of Pharmacy, Ningxia Medical University, Yinchuan 750004, China; Ningxia Engineering and Technology Research Center for Modernization of Characteristic Chinese Medicine, and Key Laboratory of Ningxia Ethnomedicine Modernization, Ministry of Education, Ningxia Medical University, Yinchuan 750004, China. Electronic address: 20070018@nxmu.edu.cn.
PMID: 39053426 DOI: 10.1016/j.biopha.2024.117199
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+), has emerged as a promising candidate for the treatment of age-related neurodegenerative disorders. NMN supplementation could restore NAD+ 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.

Keywords

Alzheimer’s disease; Autophagy; NMN; Nrf2; Oxidative stress; P-tau.

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