Atsumi Nitta

Clinical Potential of Compounds That Stimulate Nerve Growth Factor Production

Neuronal atrophy or death occurs in aging and neurological diseases. Recent research has identified some neurotrophins, such as nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), NT-4/5, and NT-6, and their involvement in various processes in neuronal growth, differentiation, and maintenance has been clarified (Leibrock et al., 1989; Hohn et al., 1990; Maisonpierre et al., 1990; Hallbook et al., 1991; Gotz et al., 1994). These neurotrophins are closely linked to injured cells and are capable of initiating a cascade of events in neurons and glia designed to prevent further damage. In many types of injury, both in the central nervous system (CNS) and in the peripheral nervous system (PNS), the induction of neurotrophins has been observed. The amounts of NGF increase after sciatic nerve lesion or transection (Lindholm et al., 1987), fimbria fornix transection (Gasser et al., 1986; Weskamp et al., 1986), electrolytic lesion of the septohippocampal pathway (Hefti, 1986; Oderfeld-Nowak et al., 1992), needle injection (Ballarin et al., 1991), denervation of the nigral dopaminernergic neuronal system (Nitta et al., 1992), limbic seizures (Gall and Issackson, 1989), transection of the optic nerve (Lu et al., 1991), excitotoxic destruction of hippocampal neurons (Bakhit et al., 1991), bilateral decortication (Lorez et al., 1988), and the evocation of aggressive behavior in adult male mice (Spillantini et al., 1989).