GDNF-Ret signaling in midbrain dopaminergic neurons and its implication for Parkinson disease

Article ID	Journal	Published Year	Pages	File Type
2047410	FEBS Letters	2015	13 Pages	PDF

Abstract

Glial cell line-derived neurotrophic factor (GDNF) and its canonical receptor Ret can signal together or independently to fulfill many important functions in the midbrain dopaminergic (DA) system. While Ret signaling clearly impacts on the development, maintenance and regeneration of the mesostriatal DA system, the physiological functions of GDNF for the DA system are still unclear. Nevertheless, GDNF is still considered to be an excellent candidate to protect and/or regenerate the mesostriatal DA system in Parkinson disease (PD). Clinical trials with GDNF on PD patients are, however, so far inconclusive. Here, we review the current knowledge of GDNF and Ret signaling and function in the midbrain DA system, and their crosstalk with proteins and signaling pathways associated with PD.

Keywords

RRF PINK1 Nurr1 Rac1 COMT VTA DJ-1 GPi CCCP GSK3β PLCγ PDZ SOS LIM NCAM EGR1 NF-κB CDC42 PTB GTPase VPS10P SHP-2 HIF-1A MEN2B SORLA TIEG FRS2 TGF-β GFRα glia cell line-derived neurotrophic factor GDNF family receptor α SRC eGFP RAF DAT ERK pKa SHC Jnk RAS 6-OHDA NGF PI3K Catechol-O-methyltransferase MPTP GDNF 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine 3′,5′-cyclic adenosine monophosphate 6-hydroxy-dopamine BDNF cAMP MAPK Phosphatidylinositol-4,5-bisphosphate 3-kinase PTEN-induced putative kinase 1 Drug addiction Dopamine transporter Parkinson disease substantia nigra Tyr RET Pleckstrin homology domain Rearranged during transfection Dopaminergic Rho Ser/Thr endoplasmatic reticulum dopaminergic system Shank3 brain derived neurotrophic factor Hypoxia-inducible factor-1alpha nerve growth factor phosphatase and tensin homolog Mouse model Enigma Neuronal cell adhesion molecule ventral tegmental area enhanced green fluorescent protein Proprotein convertases SNP Pten catecholamine carbonyl cyanide m-chlorophenyl hydrazone CoREST GABA glycosylphosphatidylinositol Glycogen synthase kinase 3β