scholarly journals Novel agonist of GDNF family ligand receptor RET for the treatment of experimental neuropathy

2016 ◽  
Author(s):  
Maxim M. Bespalov ◽  
Yulia A. Sidorova ◽  
Ilida Suleymanova ◽  
James Thompson ◽  
Oleg Kambur ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Animal Models ◽  
Cell Line ◽  
Glial Cell ◽  
Sensory Neurons ◽  
Neurotrophic Factor ◽  
Somatosensory System ◽  
Pain Symptoms ◽  
First Time

AbstractNeuropathic pain is a chronic pain condition caused by lesion or disease affecting the somatosensory system. The glial cell line-derived neurotrophic factor (GDNF) family ligands (GFLs) alleviate symptoms of NP and stimulate regeneration of sensory neurons in vivo. Here we report the development of the compound BT18 that selectively activates GFLreceptors, alleviates pain and restores damaged dorsal root ganglion (DRG) neurons in rat models of NP.Significance statementNeuropathic pain (NP) is a chronic syndrome caused by different diseases and lesions affecting nervous system. Earlier studies demonstrated that neurotrophic factors - the glial cell line-derived neurotrophic factor (GDNF) and artemin - could reverse the damage done by lesions in animal models of NP. We demonstrate for the first time that a small molecule can activate receptor of GDNF and artemin, it alleviates pain symptoms in vivo in two animal models of NP and restores to normal the molecular markers expressed in sensory neurons. This compound, termed BT18, can pave way for creating novel disease modifying therapies for NP.

scholarly journals The Glial Cell Line-Derived Neurotrophic Factor Family Receptor Components Are Differentially Regulated within Sensory Neurons after Nerve Injury

2000 ◽  
Vol 20 (1) ◽  
pp. 427-437 ◽  
Author(s):  
David L. H. Bennett ◽  
Timothy J. Boucher ◽  
Mark P. Armanini ◽  
Kris T. Poulsen ◽  
Gregory J. Michael ◽  
...  
Keyword(s):  
Cell Line ◽  
Glial Cell ◽  
Nerve Injury ◽  
Sensory Neurons ◽  
Neurotrophic Factor

Glial Cell Line-Derived Neurotrophic Factor Augments Midbrain Dopaminergic Circuits In Vivo

1995 ◽  
pp. 401-415
Author(s):  
BARRY J. HOFFER ◽  
JOHN HUDSON ◽  
GREG A. GERHARDT ◽  
MICHAEL A. HENRY ◽  
ALEX HOFFMAN ◽  
...  
Keyword(s):  
Cell Line ◽  
Glial Cell ◽  
Neurotrophic Factor

Glial cell line-derived neurotrophic factor reverses toxin-induced injury to midbrain dopaminergic neurons in vivo

1994 ◽  
Vol 182 (1) ◽  
pp. 107-111 ◽  
Author(s):  
Barry J. Hoffer ◽  
Alex Hoffman ◽  
Kate Bowenkamp ◽  
Peter Huettl ◽  
John Hudson ◽  
...  
Keyword(s):  
Cell Line ◽  
Glial Cell ◽  
Neurotrophic Factor ◽  
Dopaminergic Neurons ◽  
Midbrain Dopaminergic Neurons

Glial cell line derived neurotrophic factor (GDNF) regulates VR1 and substance P in cultured sensory neurons

Neuroreport ◽  
1999 ◽  
Vol 10 (10) ◽  
pp. 2107-2111 ◽  
Author(s):  
Patrick Ogun-Muyiwa ◽  
Rachel Helliwell ◽  
Peter McIntyre ◽  
Janet Winter
Keyword(s):  
Substance P ◽  
Cell Line ◽  
Glial Cell ◽  
Sensory Neurons ◽  
Neurotrophic Factor

In vivo regulation of glial cell line-derived neurotrophic factor-inducible transcription factor by kainic acid

Neuroscience ◽  
1999 ◽  
Vol 94 (2) ◽  
pp. 629-636 ◽  
Author(s):  
A.J. Eisch ◽  
C.-H. Lammers ◽  
S. Yajima ◽  
M.M. Mouradian ◽  
E.J. Nestler
Keyword(s):  
Transcription Factor ◽  
Cell Line ◽  
Glial Cell ◽  
Kainic Acid ◽  
Neurotrophic Factor

scholarly journals A Novel Activating Mutation in the RET Tyrosine Kinase Domain Mediates Neoplastic Transformation

2006 ◽  
Vol 20 (7) ◽  
pp. 1633-1643 ◽  
Author(s):  
Aaron Cranston ◽  
Cristiana Carniti ◽  
Sam Martin ◽  
Piera Mondellini ◽  
Yvette Hooks ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Cell Line ◽  
Glial Cell ◽  
Neurotrophic Factor ◽  
Functional Characterization ◽  
Kinase Domain ◽  
Tyrosine Kinase Domain ◽  
Exogenous Substrate

Abstract We report the finding of a novel missense mutation at codon 833 in the tyrosine kinase of the RET proto-oncogene in a patient with a carcinoma of the thyroid. In vitro experiments demonstrate that the R833C mutation induces transformed foci only when present in the long 3′ splice isoform and, in keeping with a model in which the receptor has to dimerize to be completely activated, glial cell line-derived neurotrophic factor stimulation leads the RETR833C receptor to a higher level of activation. Tyrosine kinase assays show that the RETR833C long isoform has weak intrinsic kinase activity and phosphorylation of an exogenous substrate is not elevated even in the presence of glial cell line-derived neurotrophic factor. Furthermore, the R833C mutation is capable of sustaining the transformed phenotype in vivo but does not confer upon the transformed cells the ability to degrade the basement membrane in a manner analogous to metastasis. Our functional characterization of the R833C substitution suggests that, like the V804M and S891A mutations, this tyrosine kinase mutation confers a weak activating potential upon RET. This is the first report demonstrating that the introduction of an intracellular cysteine can activate RET. However, this does not occur via dimerization in a manner analogous to the extracellular cysteine mutants.

scholarly journals Decreased expression of glial cell line-derived neurotrophic factor signaling in rat models of neuropathic pain

2003 ◽  
Vol 140 (7) ◽  
pp. 1252-1260 ◽  
Author(s):  
Masatoshi Nagano ◽  
Atsushi Sakai ◽  
Naoki Takahashi ◽  
Masahiro Umino ◽  
Koichi Yoshioka ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Cell Line ◽  
Glial Cell ◽  
Neurotrophic Factor ◽  
Rat Models ◽  
Neurotrophic Factor Signaling

scholarly journals The In Vivo Response of Stem and Other Undifferentiated Spermatogonia to the Reversible Inhibition of Glial Cell Line-Derived Neurotrophic Factor Signaling in the Adult

Stem Cells ◽  
2012 ◽  
Vol 30 (4) ◽  
pp. 732-740 ◽  
Author(s):  
Joseph Savitt ◽  
Dolly Singh ◽  
Chao Zhang ◽  
Liang-Chin Chen ◽  
Janet Folmer ◽  
...  
Keyword(s):  
Cell Line ◽  
Glial Cell ◽  
Neurotrophic Factor ◽  
Reversible Inhibition ◽  
Neurotrophic Factor Signaling
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