Neurturin, a relative of glial-cell-line-derived neurotrophic factor

Abstract

The normal development of the vertebrate nervous system entails the death of 30-70% of the neurons originally generated in most neuronal populations. This naturally occurring cell death is regulated by specific neurotrophic factors that promote neuronal survival and which are produced in limiting quantities by target cells, glial cells and neurons. These factors are also of potential utility as therapeutic agents for neurodegenerative diseases. Here we describe the purification and cloning of a new neurotrophic factor, identified on the basis of its ability to support the survival of sympathetic neurons in culture. This factor, neurturin, is structurally related to glial-cell-line-derived neurotrophic factor (GDNF). These factors can each activate the MAP kinase signalling pathway in cultured sympathetic neurons and support the survival of sympathetic neurons, as well as of sensory neurons of the nodose and dorsal root ganglia. Thus, neurturin and GDNF together now define a new family of neurotrophic factors.

Dependence receptors: a new paradigm in cell signaling and cancer therapy

“…RET was the first one ( Figure 2 and Table 1). RET is the signaling component of a multisubunit complex that functions as a receptor for glial cell line-derived neurotrophic factor (Jing et al, 1996), neurturin, artemin and persephin (Kotzbauer et al, 1996), four homologous neurotrophic factors related to the transforming growth factor-b family. The receptor complex also includes (GPI)-anchored proteins GFRa1, 2, 3 and 4 that are required for RET dimerization and dictate ligand selectivity (Baloh et al, 2000;Scott and Ibanez, 2001).…”

Receptors that mediate cellular dependence

“…53 Just as for the other dependence receptors, RET has been shown to play a role in both neural development and neoplasia: RET forms part of the receptor complex for glial-derived neurotrophic factor (GDNF) and its related trophic factors neurturin, artemin, and persephin. 54 These four trophic factors are similar to members of the transforming growth factor-b (TGF-b) family. The receptor complexes include RET and various glycosylphosphatidylinositol (GPI)-anchored proteins that are required for RET dimerization; these GPI-anchored co-receptors include GFRa-1, 2, 3, and 4.…”

Neurotrophic factors for the treatment of Parkinson's disease

“…A second member of the GFL family, neurturin, was identified for its survival-promoting effects on sympathetic neurones [78]. It was found to promote the survival of developing and mature dopaminergic neurones in vitro, These effects were similar in strength to those of GDNF [79,80].…”