was a milestone in the study of growth factors and in stimulating the search for other neurotrophic factors. It is now known that
NGF
is only one of a series of secreted factors with the ability to promote neuronal survival. The most studied class of trophic factors is the neurotrophins (
neurotrophins
). Four major neurotrophic factors have been isolated from mammals:
NGF
, brain-derived neurotrophic factor (
brain
derived
neurotrophic
factor,
BDNF
), neurotrophic factor
3
(
NT-3
) and neurotrophic factor
4/5
(
NT-4/5
). In addition,
there may
be
neurotrophic factor
6
(
NT-6
).
NGF
is widely present in humans and many species of animals. If antiserum to
NGF
is injected into a newborn animal, it can cause damage to almost all sympathetic ganglia, while injecting antiserum into a female rat can result in sensory neurologic deficits in the fetal rat. It is evident that
NGF
is necessary for the growth and survival of sympathetic and sensory neurons. It has also been shown that
NGF
increases
cAMP
levels of cholinergic neurons in the basal forebrain and striatum, increases choline acetyltransferase activity, and is important for the growth and survival of these neurons. Various
NT
have different roles in protecting neurons and preventing apoptosis, but there is some crossover and overlap. Knockout
NT-3
genes cause a marked absence of cutaneous touch
-
pressure receptors;
DBNF
-deficient mice have a reduced number of peripheral sensory neurons and severe degeneration of the vestibular ganglia.