Nerve growth factor (
NGF) is a
polypeptide that is necessary for the survival and growth of developing sympathetic and sensory neurons as well as basal forebrain cholinergic neurons in the brain. The effects of
NGF are mediated by the binding of the factor to its specific receptor present on the surface of
NGF-responsive cells. Since
NGF-responsive basal forebrain cholinergic neurons are lost in
Alzheimer's disease, treatment with
NGF may be therapeutically beneficial for the patients with this disease. Our studies were focused on the purification, amino acid sequence,
enzyme immunoassay (EIA),
NGF-biosynthesizing cells, regulation of the biosynthesis, compounds stimulating
NGF-biosynthesis/secretion, etc. The major results obtained are summarized as follows: 1) We purified NGFs from
snake venoms and determined their amino acid sequences. Among them, Crotalus adamanteus-and Vipera russelli-NGFs were
glycoproteins. 2) We developed highly sensitive (0.03-0.05 pg/tube or bead), simple, and reliable EIA systems for NGFs and NT-3. 3)
Catecholamine, its derivatives, p-
quinone derivatives,
nicotine,
nicotine derivatives,
coenzymes, etc. enhanced the
NGF-biosynthesis/secretion of fibroblasts and astrocytes by increasing their cellular content of
NGF mRNA. 4) Basal forebrain-lesioned rats (an animal model of
amnesia) administered 6-(4-hydroxybutyl)-2,3,5-trimethyl-1,4-
benzoquinone (TMQ) orally showed improvement not only their
NGF level and
choline acetyltransferase (CAT) activity in the brain but also their memory and learning. 5)
Interleukins (IL)-4 and -5 significantly increased the amounts of
NGF secreted by mouse astrocytes; whereas IL-2, -3, and -6 had no significant effect. 6)
Interferons-beta and -lambda inhibited the
DNA- and
NGF-synthesis in growing astrocytes cultured from neonatal mouse brain but they had no effect on the
NGF-synthesis/secretion in quiescent astrocytes. 7) Alkylcatechols regulated the
NGF gene expression in astrocytes via both
protein kinase C- and cAMP-independent mechanisms.