Neuritin: A therapeutic candidate for promoting axonal regeneration

Abstract

Following injury, the axons of the mammalian central nervous system do not regenerate. Many studies have aimed at understanding the mechanisms that prevent axonal regeneration and at designing ways to overcome the obstacles preventing axonal regrowth. These studies have identified numerous proteins as promoters of axonal regeneration. In this minireviews, we focus on neuritin as a therapeutic candidate for promoting axonal regeneration. Neuritin was first identified as a neuronal-activity-inducible gene product in the rat brain. The overexpression of neuritin in neurons or the application of neuritin to neurons induces neuritogenesis, neurite arborization, and axonal elongation both in vitro and in vivo. These morphological changes are often observed during the first step of axonal regeneration. Indeed, neuritin expression increases during axonal regeneration in the peripheral nervous system (PNS). Conversely, in a mouse model of diabetes mellitus, neuritin expression decreases in the PNS, and this reduced expression may result in deficient axonal regeneration. Neuritin is induced in the hippocampal dentate gyrus after temporal lobe epilepsy or brain ischemia; however, in these conditions, neuritin induction may exacerbate brain dysfunction through mossy fiber sprouting. Together, these findings support the hypothesis that tightly controlled regulation of neuritin may be required for the treatment of each unique axonal pathology.

Keywords: Axonal regeneration, Neuronal development, Axonal injury, Neuritogenesis, Epilepsy

Core tip: Neuritin has been shown to be an activity-regulated protein in neurons. Its expression also increases after neuronal damage. Neuritin induces neuritogenesis, arborization, and axonal elongation. These functions may be beneficial for axonal regeneration after nerve injury. Here, we review neuritin as a therapeutic candidate for promoting axonal regeneration in the peripheral and central nervous systems. We also discuss the possible involvement of neuritin in mossy fiber sprouting after epileptic seizures or brain ischemia.