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A Peptide Uncoupling BDNF Receptor TrkB from Phospholipase Cγ1 Prevents Epilepsy Induced by Status Epilepticus.

dc.contributor.author Gu, Bin
dc.contributor.author Huang, Yang Zhong
dc.contributor.author He, Xiao-Ping
dc.contributor.author Joshi, Rasesh B
dc.contributor.author Jang, Wonjo
dc.contributor.author McNamara, James O
dc.coverage.spatial United States
dc.date.accessioned 2016-04-22T18:07:56Z
dc.date.issued 2015-11-04
dc.identifier http://www.ncbi.nlm.nih.gov/pubmed/26481038
dc.identifier S0896-6273(15)00821-1
dc.identifier.uri https://hdl.handle.net/10161/11838
dc.description.abstract The BDNF receptor tyrosine kinase, TrkB, underlies nervous system function in both health and disease. Excessive activation of TrkB caused by status epilepticus promotes development of temporal lobe epilepsy (TLE), revealing TrkB as a therapeutic target for prevention of TLE. To circumvent undesirable consequences of global inhibition of TrkB signaling, we implemented a novel strategy aimed at selective inhibition of the TrkB-activated signaling pathway responsible for TLE. Our studies of a mouse model reveal that phospholipase Cγ1 (PLCγ1) is the dominant signaling effector by which excessive activation of TrkB promotes epilepsy. We designed a novel peptide (pY816) that uncouples TrkB from PLCγ1. Treatment with pY816 following status epilepticus inhibited TLE and prevented anxiety-like disorder yet preserved neuroprotective effects of endogenous TrkB signaling. We provide proof-of-concept evidence for a novel strategy targeting receptor tyrosine signaling and identify a therapeutic with promise for prevention of TLE caused by status epilepticus in humans.
dc.language eng
dc.publisher Elsevier BV
dc.relation.ispartof Neuron
dc.relation.isversionof 10.1016/j.neuron.2015.09.032
dc.subject Amino Acid Sequence
dc.subject Animals
dc.subject Epilepsy
dc.subject Female
dc.subject Hippocampus
dc.subject Humans
dc.subject Male
dc.subject Mice
dc.subject Mice, 129 Strain
dc.subject Mice, Inbred C57BL
dc.subject Mice, Transgenic
dc.subject Molecular Sequence Data
dc.subject Peptide Fragments
dc.subject Phospholipase C gamma
dc.subject Rats
dc.subject Rats, Sprague-Dawley
dc.subject Receptor, trkB
dc.subject Status Epilepticus
dc.subject Uncoupling Agents
dc.title A Peptide Uncoupling BDNF Receptor TrkB from Phospholipase Cγ1 Prevents Epilepsy Induced by Status Epilepticus.
dc.type Journal article
duke.contributor.id Huang, Yang Zhong|0305617
duke.contributor.id He, Xiao-Ping|0103993
duke.contributor.id McNamara, James O|0114455
pubs.author-url http://www.ncbi.nlm.nih.gov/pubmed/26481038
pubs.begin-page 484
pubs.end-page 491
pubs.issue 3
pubs.organisational-group Basic Science Departments
pubs.organisational-group Clinical Science Departments
pubs.organisational-group Duke
pubs.organisational-group Duke Institute for Brain Sciences
pubs.organisational-group Institutes and Provost's Academic Units
pubs.organisational-group Neurobiology
pubs.organisational-group Neurology
pubs.organisational-group Neurology, Epilepsy and Sleep
pubs.organisational-group Pharmacology & Cancer Biology
pubs.organisational-group School of Medicine
pubs.organisational-group University Institutes and Centers
pubs.publication-status Published
pubs.volume 88
dc.identifier.eissn 1097-4199


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