Growth factors - Pharmaceutical Biotechnology: Concepts and Aapplications - page 288

and fi broblasts. Given such activities, it is not surprising that the major physiological impact of
TGF-βs appears to relate to:

• tissue remodelling;

• wound repair;

• haemopoiesis.

Such activities render them potentially useful therapeutic agents, and several are being assessed
medically.

10.3.7 Neurotrophic factors

Neurotrophic factors constitute a group of cytokines that regulate the development, maintenance
and survival of neurons, both in the central and peripheral nervous systems (Table 10.12). Although
the fi rst member of this family (NGF) was discovered more than 50 years ago, it is only in the last
decade that the other members have been identifi ed and characterized. The major subfamily of
neurotrophic factors is the neurotrophins.
The original understanding of the term 'neurotrophic factor' was that of a soluble agent found in
limiting quantities in the environment of sensitive neurons, and being generally manufactured by
the neuronal target cells. It specifi cally promoted the growth and maintenance of those neurons.
This description is now considered to be oversimplistic. Many neurotrophic factors are also syn-
thesized by non-nerve target cells, and infl uence cells other than neurons (e.g. NGF is synthesized
by mast cells and infl uences various cells of the immune system). Furthermore, various cytokines
(including several growth factors; Table 10.12), discovered because of their ability to stimulate the
growth of non-neuronal cells, are now also known to infl uence neuronal cells.
Each neurotrophic factor infl uences the growth and development of a specifi c group of neuronal
types, with some cells being sensitive to several such factors. Many sustain specifi c neuronal
populations whose death underlines various neurodegenerative diseases. This raises the possibility
that these regulatory molecules may be of benefi t in treating such diseases. Results from early
clinical trials have been at best mixed, but many remain optimistic that neurotrophic factors may
provide future effective treatments for some currently incurable neurodegenerative conditions.

Table 10.12 Molecules displaying neurotrophic activity
in vivo and/or with neurons in culture

NGF FGFs

BDNF PDGF

Neurotrophin-3 (NT-3) IGF-I and -II

Neurotrophin-4/5 (NT 4/5) TGF-β1

Neurotrophin-6 (NT-6) GM-CSF

CNTF EPO

GDNF LIF