Nicotinamide phosphoribosyltransferase‑related signaling pathway in early Alzheimer's disease mouse models

• Published in: Molecular medicine reports Vol. 20; no. 6; pp. 5163 - 5171
• Main Authors: Xing, Sanli, Hu, Yiran, Huang, Xujiao, Shen, Dingzhu, Chen, Chuan
• Format: Journal Article
• Language: English
• Published: Greece Spandidos Publications 01.12.2019; Spandidos Publications UK Ltd; D.A. Spandidos
• Subjects: Acrylamides - antagonists & inhibitors; Acrylamides - pharmacology; Adenine; Advertising executives; Age; Aging; Alzheimer Disease - metabolism; Alzheimer's disease; Amyloid - metabolism; Analysis; Animal models; Animals; Behavior, Animal; Brain research; Central nervous system; Cognitive ability; Cognitive disorders; Cytokines - drug effects; Cytokines - genetics; Cytokines - metabolism; Dementia; Dementia disorders; Disease Models, Animal; Energy; Enzymes; Genetic engineering; Hippocampus - drug effects; Homeostasis; Laboratory animals; Learning - drug effects; Male; Medical research; Memory - drug effects; Metabolism; Mice; Mice, Inbred C57BL; Mice, Transgenic; NAD; NAD - antagonists & inhibitors; NAD - metabolism; NAD - pharmacology; NADH; Nervous system; Neurodegeneration; Neurodegenerative diseases; Neurons; Niacinamide; Nicotinamide; Nicotinamide phosphoribosyltransferase; Nicotinamide Phosphoribosyltransferase - drug effects; Nicotinamide Phosphoribosyltransferase - genetics; Nicotinamide Phosphoribosyltransferase - metabolism; Pathogenesis; Pharmaceutical industry; Phosphoribosyltransferase; Phosphorylation; Piperidines - antagonists & inhibitors; Piperidines - pharmacology; Presenilin 1; Proteins; Purines; Rodents; Senile plaques; Signal transduction; Signal Transduction - physiology; Sirtuin 1 - metabolism; Spatial discrimination learning; Spatial memory; Studies; Transgenic animals; Transgenic mice; Video recorders; China; Germany
• ISSN: 1791-2997; 1791-3004
• DOI: 10.3892/mmr.2019.10782

Alzheimer's disease (AD) is a neurodegenerative disease of the central nervous system that is characterized by progressive cognitive dysfunction and which ultimately leads to dementia. Studies have shown that energy dysmetabolism contributes significantly to the pathogenesis of a variety of aging‑associated diseases and degenerative diseases of the nervous system, including AD. One focus of research thus has been how to regulate the expression of nicotinamide phosphoribosyltransferase (NAMPT) to prevent against neurodegenerative diseases. Therefore, the present study used 6‑month‑old APPswe/PS1ΔE9 (APP/PS1) transgenic mice as early AD mouse models and sought to evaluate nicotinamide adenine dinucleotide (NAD+) and FK866 (a NAMPT inhibitor) treatment in APP/PS1 mice to study NAMPT dysmetabolism in the process of AD and elucidate the underlying mechanisms. As a result of this treatment, the expression of NAMPT decreased, the synthesis of ATP and NAD+ became insufficient and the NAD+/NADH ratio was reduced. The administration of NAD+ alleviated the spatial learning and memory of APP/PS1 mice and reduced senile plaques. Administration of NAD+ may also increase the expression of the key protein NAMPT and its related protein sirtuin 1 as well as the synthesis of NAD+. Therefore, increasing NAMPT expression levels may promote NAD+ production. Their regulation could form the basis for a new therapeutic strategy.