Search results for "GDNF"

The cytoprotective protein MANF promotes neuronal survival independently from its role as a GRP78 cofactor

2021

Mesencephalic astrocyte-derived neurotrophic factor (MANF) is an endoplasmic reticulum (ER)-stress-regulated protein exhibiting cytoprotective properties through a poorly understood mechanism in various in vitro and in vivo models of neuronal and non-neuronal damage. Although initially characterized as a secreted neurotrophic factor for midbrain dopamine neurons, MANF has recently gained more interest for its intracellular role in regulating the ER homeostasis, including serving as a cofactor of the chaperone glucose-regulated protein 78 (GRP78). We aimed for a better understanding of the neuroprotective mechanisms of MANF. Here we show for the first time that MANF promotes the survival of …

Metabotropic glutamate (mGLU2/3) receptor agonist LY379268 stimulates the production of glial cell line-derived neurotrophic factor (GDNF) in the mou…

2009

mGluR2/3 agonist LY379268, by enhancing the production of GDNF, induces a time-related phosphorylation of RET receptor and intracellular signaling Er…

2011

In the present study we aimed to verify if the enhancement of glial cell line-derived neurotrophic factor (GDNF) production in mouse striatum following treatment with LY379268 may also induce in the nigrostriatal system a time-related activation of RET receptor and its specific intracellular signaling. For this purpose, we have investigated the effects of LY379268 treatment on RET phosphorylation at the Tyr1062 and on downstream signaling Erk1/2, Akt and PLCγ1 pathway activation. The results showed that treatment with LY379268 (3 mg/kg) induces a significant increase of GDNF levels and time-related RET and Erk1/2 phosphorylation in the striatum. These increases were detected at 24 h and 48 …

Time-course of GDNF and its receptor expression after brain injury in the rat

2008

Abstract The aim of the present work was to perform, by in situ hybridization, a time-course analysis of the glial cell line-derived neurotrophic factor (GDNF) and its receptor mRNA expression in two models of brain injury in the rat: (a) excitotoxic lesion by ibotenic acid injection in the hippocampal formation; (b) mechanical lesion by needle insertion through the cerebral cortex including the white matter of the corpus callosum. The time-course analysis, ranging from 6 h to 8 days, showed that the GDNF and its receptor (RET, GFRα-1 and GFRα-2) mRNA expressions were differentially up-regulated in both models of lesion. This in vivo regulation of the GDNF and its receptor mRNA expression i…

Analysis of the RET, GDNF, EDN3, and EDNRB genes in patients with intestinal neuronal dysplasia and Hirschsprung disease

2001

BACKGROUNDHirschsprung disease (HSCR) is a frequent congenital disorder with an incidence of 1 in 5000 live births, characterised by the absence of parasympathetic intramural ganglion cells in the hindgut resulting in intestinal obstruction in neonates and severe constipation in infants and adults. Intestinal neuronal dysplasia (IND) shares clinical features with HSCR but the submucosal parasympathetic plexus is affected. IND has been proposed as one of the most frequent causes of chronic constipation and is often associated with HSCR.METHODSWe examined 29 patients diagnosed with sporadic HSCR, 20 patients with IND, and 12 patients with mixed HSCR/IND for mutations in the coding regions of …

Expression of neurotrophins, GDNF, and their receptors in rat thyroid tissue

1999

Levels of mRNA for neurotrophins (brain-derived neurotrophic factor, BDNF; neurotrophin 3, NT-3; neurotrophin 4, NT-4) and their receptors (trkA, trkB, trkC) and for glial cell line-derived neurotrophic factor (GDNF) and its receptors (ret, GDNFR-alpha) were measured in rat thyroid tissue by ribonuclease protection assays. In thyroid tissue the NT-3 mRNA level was threefold lower and the NT-4 mRNA level sixfold higher than those detected in adult rat hippocampus, while BDNF mRNA was undetectable. Very low levels of mRNA for truncated trkB and trkC receptors and no catalytic trkA, trkB or trkC were found. In conclusion NT-3 and NT-4, but not the corresponding functional receptors, are expres…

Advancing stem cells: New therapeutic strategies for treating central nervous system disorders

2018

In this special issue, we explore new methods and knowledge to improve stem cell transplantation in diseases and conditions such as stroke, PD, and depression. Advancing the conventional idea regarding cell replacement in stem cell therapy, stem cells may also transfer healthy mitochondria to diseased ischemic neurons in stroke and improve the therapeutic time window of tissue plasminogen activator (tPA) in a conjunctive therapy for stroke, and human Wharton’s Jelly-derived mesenchymal stromal cells (hWJ-MSCs) may rely mainly on trophic factor secretion to induce neuroprotective effects. In addition, trophic factors such as neurotrophin-4/5 (NT-4/5) and glial cell line-derived neurotrophic …