Nicotinamide mononucleotide inhibits JNK activation to reverse Alzheimer disease.
Amyloid-β (Aβ) oligomers have been accepted as major neurotoxic agents in the therapy of Alzheimer's disease (AD). It has been shown that the activity of nicotinamide adenine dinucleotide (NAD+) is related with the decline of Aβ toxicity in AD. Nicotinamide mononucleotide (NMN), the important precursor of NAD+, is produced during the reaction of nicotinamide phosphoribosyl transferase (Nampt). This study aimed to figure out the potential therapeutic effects of NMN and its underlying mechanisms in APPswe/PS1dE9 (AD-Tg) mice. We found that NMN gave rise to a substantial improvement in behavioral measures of cognitive impairments compared to control AD-Tg mice. In addition, NMN treatment significantly decreased β-amyloid production, amyloid plaque burden, synaptic loss, and inflammatory responses in transgenic animals. Mechanistically, NMN effectively controlled JNK activation. Furthermore, NMN potently progressed nonamyloidogenic amyloid precursor protein (APP) and suppressed amyloidogenic APP by mediating the expression of APP cleavage secretase in AD-Tg mice. Based on our findings, it was suggested that NMN substantially decreases multiple AD-associated pathological characteristically at least partially by the inhibition of JNK activation.
Department of Neurology, YangPu Hospital, Tongji University School of Medicine, Shanghai 200092, China.
Zhiwen
Z
Yao
Department of Neurology, YangPu Hospital, Tongji University School of Medicine, Shanghai 200092, China.
Wenhao
W
Yang
Department of Neurology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, 210011, China.
Zhiqiang
Z
Gao
Department of Neurology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, 210011, China. Electronic address: pengjianj@126.com.
Peng
P
Jia
D000544:Alzheimer Disease / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology / Q000523:psychology; D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D003072:Cognition Disorders / Q000188:drug therapy / Q000523:psychology; D004789:Enzyme Activation; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D008568:Memory / Q000187:drug effects; D008822:Mice, Transgenic; D009537:Nicotinamide Mononucleotide / Q000627:therapeutic use*; D058225:Plaque, Amyloid / Q000473:pathology; D065853:Spatial Learning / Q000187:drug effects; D013569:Synapses / Q000473:pathology
D016564:Amyloid beta-Protein Precursor; D009537:Nicotinamide Mononucleotide; D048031:JNK Mitogen-Activated Protein Kinases; D053829:Amyloid Precursor Protein Secretases
Alzheimer disease; Amyloid-β; JNK activation; Nicotinamide mononucleotide