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.

Immunization with neural‐derived peptides increases neurogenesis in rats with chronic spinal cord injury

“…Nevertheless, recent reports suggest that neurogenesis in the adult state can be found in other regions of the CNS, such as the amygdala, neocortex, 20 cerebellum, striatum, and substantia nigra 21,22 . Additionally, neurogenesis is also amplified after mechanical damage due to traumatic brain injury 23 or SCI 24 …”

Cerebral Organoids Repair Ischemic Stroke Brain Injury

“…All scale bars are as shown angiogenesis [2,29]. Neurogenesis is an endogenous process involving proliferation, differentiation, and migration of NPCs/NSCs in the hippocampal subgranular zone (SGZ) and subventricular zone (SVZ), which is important for replacing gradual neuron loss and maintaining specific neuronal function throughout life [30,31].…”

Organoid technology for brain and therapeutics research

“…Our group has done much work in identifying therapeutic targets and screening effective neuroprotective drugs against stroke . Recently, we have demonstrated that nicotinamide phosphoribosyltransferase‐NAD cascade which is particularly important for the proliferation, self‐renewal, and differentiation of neural stem cells can promote regenerative neurogenesis after ischemic stroke . In addition to promoting tissue regeneration by stimulating endogenous stem cells, progress in stem cell transplantation also enhances the development of regenerative medicine …”

“…[43][44][45] Recently, we have demonstrated that nicotinamide phosphoribosyltransferase-NAD cascade which is particularly important for the proliferation, self-renewal, and differentiation of neural stem cells can promote regenerative neurogenesis after ischemic stroke. [46][47][48] In addition to promoting tissue regeneration by stimulating endogenous stem cells, progress in stem cell transplantation also enhances the development of regenerative medicine. 49,50 As organoids contain stem or progenitor cells and have the potential to develop into whole organs, organoids can provide a source of autologous cell and tissues for transplantation.…”