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

  title={Neurturin, a relative of glial-cell-line-derived neurotrophic factor},
  author={Paul T Kotzbauer and Patricia A. Lampe and Robert O. Heuckeroth and Judith P Golden and Douglas J. Creedon and Eugene M. Johnson and Jeffrey D. Milbrandt},
THE normal development of the vertebrate nervous system entails the death of 30–70% of the neurons originally generated in most neuronal populations1. 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 diseases2. Here we describe the purification and cloning of… 

Neurotrophic Roles of GDNF and Related Factors

The transforming growth factor-β (TGF-β) superfamily harbors a number of examples to illustrate how growth factors with long-established functions in growth and differentiation control have unveiled astonishing capacities in regulating the survival and differentiation of neurons.

Other neurotrophic factors: Glial cell line‐derived neurotrophic factor (GDNF)

Recent transgenic and organ culture experiments have clearly demonstrated that GDNF is a mesenchyme‐derived signaling molecule for the promotion of ureteric branching in kidney development.

Regulation of neural development by glial cell line-derived neurotrophic factor family ligands

  • H. Enomoto
  • Biology, Chemistry
    Anatomical science international
  • 2005
The deciphering of GDNF family ligand signaling in neural cells promises to provide vital new insights into the development and pathology of the nervous system.

Expression of neurturin, GDNF, and their receptors in the adult mouse CNS

The pattern of GF factor and receptor expression in the adult brain suggests a role for these factors in maintaining neuronal circuits in the mature CNS.

Neurturin Exerts Potent Actions on Survival and Function of Midbrain Dopaminergic Neurons

It is suggested that neurturin (NTN), a homolog of GDNF, is expressed in the nigrostriatal system, and that NTN exerts potent effects on survival and function of midbrain DA neurons and point to the possibility that GDNF and NTN may exert redundant trophic influences on nigral DA neurons acting via a receptor complex that includes GFRα1.

Biology of glial cell-line derived neurotrophic factor

The present review will concentrate on GDNF, the most extensively studied of the four proteins, and the known properties of the other three trophic factors and their comparison to GDNF will be discussed at the end of the chapter.

Neurturin is a neuritogenic but not a survival factor for developing and adult central noradrenergic neurons

It is found that tyrosine hydroxylase (TH)‐positive neurons in the LC express both GFRα1 and 2 receptors in a developmentally regulated fashion, suggesting a function for their preferred ligands: GDNF and NTN, respectively.



GDNF: a glial cell line-derived neurotrophic factor for midbrain dopaminergic neurons.

In embryonic midbrain cultures, recombinant human GDNF promoted the survival and morphological differentiation of dopaminergic neurons and increased their high-affinity dopamine uptake and did not increase total neuron or astrocyte numbers or transmitter uptake.

GDNF: a potent survival factor for motoneurons present in peripheral nerve and muscle.

Glial cell line-derived neurotrophic factor (GDNF), originally identified as a trophic factor specific for dopaminergic neurons, was found to be 75-fold more potent than the neurotrophins in supporting the survival of purified embryonic rat motoneurons in culture and to be a good candidate for treatment of motoneuron disease.

Glial cell line‐derived neurotrophic factor (GDNF), a new neurotrophic factor for motoneurones

The present results indicate that GDNF may have a therapeutic potential in human motoneurone diseases such as amyotrophic lateral sclerosis.

Functional receptor for GDNF encoded by the c-ret proto-oncogene

It is shown that GDNF binds to, and induces tyrosine phosphorylation of, the product of the c-ret proto-oncogene, an orphan receptor tyrosin kinase, in a GDNF responsive motor-neuron cell line, which encodes a functional receptor for GDNF that may mediate its neurotrophic effects on motor and dopaminergic neurons.

In vivo neurotrophic effects of GDNF on neonatal and adult facial motor neurons

It is found that GDNF is retrogradely transported, in a receptor-mediated fashion, by spinal cord motor neurons in neonatal rats, and is the most potent motor neuron trophic factor found so far.

Developing motor neurons rescued from programmed and axotomy-induced cell death by GDNF

Glial-cell-line-derived neurotrophic factor (GDNF), a potent neurotrophicfactor that enhances survival of mammalian midbrain dopaminergic neurons16,17, rescues developing avian motor neurons from natural programmed cell death in vivo and promotes the survival of enriched populations of cultured motor neurons.

Mesencephalic dopaminergic neurons protected by GDNF from axotomy-induced degeneration in the adult brain

It is reported that axotomy resulted in loss of half the tyrosine hydroxylase-expressing neurons in the substantia nigra, which suggests that GDNF or related molecules may be useful for the treatment of Parkinson's disease.

Characterization of a multicomponent receptor for GDNF

It is demonstrated that physiological responses to GDNF require the presence of a novel glycosyl-phosphatidylinositol (GPI)-linked protein (designated GDNFR-α) that is expressed on GDNF-responsive cells and binds GDNF with a high affinity, which supports the hypothesis that GDNF uses a multi-subunit receptor system in which GDN FR-α and Ret function as the ligand-binding and signalling components.

Neurotrophic factor therapy for nervous system degenerative diseases.

  • F. Hefti
  • Medicine, Biology
    Journal of neurobiology
  • 1994
The ability of neurotrophic factors to regulate developmental neuronal survival and adult nervous system plasticity suggests the use of these molecules to treat neurodegeneration associated with