Roles of transforming growth factor-alpha and related molecules in the nervous system

The epidermal growth factor (EGF) family of polypeptides is regulators for tissue development and repair, and is characterized by the fact that their mature forms are proteolytically derived from their integral membrane precu rsors. This article reviews roles of the prominent members of the EGF famil y (EGF, transforming growth factor-alpha [TGF-alpha] and heparin-binding EG F [HB-EGF]) and the related neuregulin family in the nerve system. These po lypeptides, produced by neurons and glial cells, play an important role in the development of the nervous system, stimulating proliferation, migration , and differentiation of neuronal, glial, and Schwann precursor cells. Thes e peptides are also neurotrophic, enhancing survival and inhibiting apoptos is of post-mitotic neurons, probably acting directly through receptors on n eurons, or indirectly via stimulating glial proliferation and glial synthes is of other molecules such as neurotrophic factors. TGF-alpha, EGF, and neu regulins are involved in mediating glial-neuronal and axonal-glial interact ions, regulating nerve injury responses, and participating in injury-associ ated astrocytic gliosis, brain tumors, and other disorders of the nerve sys tem. Although the collective roles of the EGF family (as well as those of t he neuregulins) are shown to be essential for the nervous system, redundanc y may exist among members of the EGF family.