title: Targeting Nicotinamide Phosphoribosyltransferase as a Potential Therapeutic Strategy to Restore Adult Neurogenesis.
abstract: Adult neurogenesis is the process of generating new neurons throughout life in the olfactory bulb and hippocampus of most mammalian species, which is closely related to aging and disease. Nicotinamide phosphoribosyltransferase (NAMPT), also an adipokine known as visfatin, is the rate-limiting enzyme for mammalian nicotinamide adenine dinucleotide (NAD) salvage synthesis by generating nicotinamide mononucleotide (NMN) from nicotinamide. Recent findings from our laboratory and other laboratories have provided much evidence that NAMPT might serve as a therapeutic target to restore adult neurogenesis. NAMPT-mediated NAD biosynthesis in neural stem/progenitor cells is important for their proliferation, self-renewal, and formation of oligodendrocytes in vivo and in vitro. Therapeutic interventions by the administration of NMN, NAD, or recombinant NAMPT are effective for restoring adult neurogenesis in several neurological diseases. We summarize adult neurogenesis in aging, ischemic stroke, traumatic brain injury, and neurodegenerative disease and review the advances of targeting NAMPT in restoring neurogenesis. Specifically, we provide emphasis on the P7C3 family, a class of proneurogenic compounds that are potential NAMPT activators, which might shed light on future drug development in neurogenesis restoration.
authors.affiliation: Department of Pharmacology, Second Military Medical University, Shanghai, China.
authors.forename: Shu-Na
authors.initials: SN
authors.lastname: Wang
authors.affiliation: Department of Pharmacology, Second Military Medical University, Shanghai, China.
authors.forename: Tian-Ying
authors.initials: TY
authors.lastname: Xu
authors.affiliation: Department of Cell Biology, Second Military Medical University, Shanghai, China.
authors.forename: Wen-Lin
authors.initials: WL
authors.lastname: Li
authors.affiliation: Department of Pharmacology, Second Military Medical University, Shanghai, China.|Center of Stroke, Beijing Institute for Brain Disorders, Beijing, China.
authors.forename: Chao-Yu
authors.initials: CY
authors.lastname: Miao
mesh_terms: D000375:Aging / Q000187:drug effects / Q000502:physiology; D000818:Animals; D006801:Humans; D009243:NAD / Q000494:pharmacology / Q000627:therapeutic use; D009422:Nervous System Diseases / Q000188:drug therapy* / Q000201:enzymology; D055495:Neurogenesis / Q000187:drug effects* / Q000502:physiology; D009537:Nicotinamide Mononucleotide / Q000494:pharmacology / Q000627:therapeutic use; D054409:Nicotinamide Phosphoribosyltransferase / Q000378:metabolism* / Q000627:therapeutic use*
chemical_list: D009243:NAD; D009537:Nicotinamide Mononucleotide; D054409:Nicotinamide Phosphoribosyltransferase
keywords: Adult neurogenesis; Neurological disease; Nicotinamide adenine dinucleotide; Nicotinamide mononucleotide; Nicotinamide phosphoribosyltransferase