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Advances in research of GDNF ligands and GDNF receptors for treatment of diseases

Chuanyin Wei, Limei Wang, Xuehong Chen, Chang‐Lin Lu, Meiyu Geng

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Abstract

Glial cell line-derived neurotrophic factor (GDNF) possesses potent and specific ability to promote the survival and morphological differentiation of dopaminergic neurons and motoneurons in embryonic midbrain cultures. GDNF is an attractive therapeutic candidate for the treatment of neurodegenerative diseases and nerve injuries. The neurotrophic and morphogenic activities of GDNF are mediated by its interaction with a multicomponent receptor complex formed by the Ret receptor tyrosine kinase and a glycosylphosphatidylinositol (GPI)-anchored ‘accessory’ receptor, GDNF family receptor α-1 (GFRα1). The GDNF ligands include neurturin (NRTN), persephin (PSPN) and ARTNemin (ARTN) and they are structurally and functinally correlated. Recent researches found that GDNF played an important therapeutic role in many diseases. This paper reviews the interaction, signaling transduction and therapeutic prospect of GDNF ligands and their receptors.

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What this paper is about

Glial cell line-derived neurotrophic factor (GDNF) possesses potent and specific ability to promote the survival and morphological differentiation of dopaminergic neurons and motoneurons in embryonic midbrain cultures. GDNF is an attractive therapeutic candidate for the treatment of neurodegenerative diseases and nerve injuries. The neurotrophic and morphogenic activities of GDNF are mediated by its interaction with a multicomponent receptor complex formed by the Ret receptor tyrosine kinase and a glycosylphosphatidylinositol (GPI)-anchored ‘accessory’ receptor, GDNF family receptor α-1 (GFRα1). The GDNF ligands include neurturin (NRTN), persephin (PSPN) and ARTNemin (ARTN) and they are structurally and functinally correlated. Recent researches found that GDNF played an important therapeutic role in many diseases. This paper reviews the interaction, signaling transduction and therapeutic prospect of GDNF ligands and their receptors.

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Available abstract

Glial cell line-derived neurotrophic factor (GDNF) possesses potent and specific ability to promote the survival and morphological differentiation of dopaminergic neurons and motoneurons in embryonic midbrain cultures. GDNF is an attractive therapeutic candidate for the treatment of neurodegenerative diseases and nerve injuries. The neurotrophic and morphogenic activities of GDNF are mediated by its interaction with a multicomponent receptor complex formed by the Ret receptor tyrosine kinase and a glycosylphosphatidylinositol (GPI)-anchored ‘accessory’ receptor, GDNF family receptor α-1 (GFRα1). The GDNF ligands include neurturin (NRTN), persephin (PSPN) and ARTNemin (ARTN) and they are structurally and functinally correlated. Recent researches found that GDNF played an important therapeutic role in many diseases. This paper reviews the interaction, signaling transduction and therapeutic prospect of GDNF ligands and their receptors.

Key concepts: Glial cell line-derived neurotrophic factor, Neurturin, GDNF family of ligands, Neurotrophic factors, Proto-Oncogene Proteins c-ret, Receptor, Biology, Neuroscience

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