Skip to main content
Duke University Libraries
DukeSpace Scholarship by Duke Authors
  • Login
  • Ask
  • Menu
  • Login
  • Ask a Librarian
  • Search & Find
  • Using the Library
  • Research Support
  • Course Support
  • Libraries
  • About
View Item 
  •   DukeSpace
  • Duke Scholarly Works
  • Scholarly Articles
  • View Item
  •   DukeSpace
  • Duke Scholarly Works
  • Scholarly Articles
  • View Item
JavaScript is disabled for your browser. Some features of this site may not work without it.

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

Thumbnail
View / Download
3.5 Mb
Date
2015-11-04
Authors
Gu, Bin
Huang, Yang Zhong
He, Xiao-Ping
Joshi, Rasesh B
Jang, Wonjo
McNamara, James O
Repository Usage Stats
198
views
200
downloads
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.
Type
Journal article
Subject
Amino Acid Sequence
Animals
Epilepsy
Female
Hippocampus
Humans
Male
Mice
Mice, 129 Strain
Mice, Inbred C57BL
Mice, Transgenic
Molecular Sequence Data
Peptide Fragments
Phospholipase C gamma
Rats
Rats, Sprague-Dawley
Receptor, trkB
Status Epilepticus
Uncoupling Agents
Permalink
https://hdl.handle.net/10161/11838
Published Version (Please cite this version)
10.1016/j.neuron.2015.09.032
Publication Info
Gu, Bin; Huang, Yang Zhong; He, Xiao-Ping; Joshi, Rasesh B; Jang, Wonjo; & McNamara, James O (2015). A Peptide Uncoupling BDNF Receptor TrkB from Phospholipase Cγ1 Prevents Epilepsy Induced by Status Epilepticus. Neuron, 88(3). pp. 484-491. 10.1016/j.neuron.2015.09.032. Retrieved from https://hdl.handle.net/10161/11838.
This is constructed from limited available data and may be imprecise. To cite this article, please review & use the official citation provided by the journal.
Collections
  • Scholarly Articles
More Info
Show full item record

Scholars@Duke

Xiao-Ping He

Assistant Professor of Neurology
This author no longer has a Scholars@Duke profile, so the information shown here reflects their Duke status at the time this item was deposited.

Yangzhong Huang

Assistant Research Professor of Neurobiology
McNamara

James O'Connell McNamara Sr.

Duke School of Medicine Distinguished Professor in Neuroscience
Our goal is to elucidate the cellular and molecular mechanisms underlying epileptogenesis, the process by which a normal brain becomes epileptic.  The epilepsies constitute a group of common, serious neurological disorders, among which temporal lobe epilepsy (TLE) is the most prevalent and devastating. Many patients with severe TLE experienced an episode of prolonged seizures (status epilepticus, SE) years prior to the onset of TLE. Because induction of SE alone is
Alphabetical list of authors with Scholars@Duke profiles.
Open Access

Articles written by Duke faculty are made available through the campus open access policy. For more information see: Duke Open Access Policy

Rights for Collection: Scholarly Articles


Works are deposited here by their authors, and represent their research and opinions, not that of Duke University. Some materials and descriptions may include offensive content. More info

Make Your Work Available Here

How to Deposit

Browse

All of DukeSpaceCommunities & CollectionsAuthorsTitlesTypesBy Issue DateDepartmentsAffiliations of Duke Author(s)SubjectsBy Submit DateThis CollectionAuthorsTitlesTypesBy Issue DateDepartmentsAffiliations of Duke Author(s)SubjectsBy Submit Date

My Account

LoginRegister

Statistics

View Usage Statistics
Duke University Libraries

Contact Us

411 Chapel Drive
Durham, NC 27708
(919) 660-5870
Perkins Library Service Desk

Digital Repositories at Duke

  • Report a problem with the repositories
  • About digital repositories at Duke
  • Accessibility Policy
  • Deaccession and DMCA Takedown Policy

TwitterFacebookYouTubeFlickrInstagramBlogs

Sign Up for Our Newsletter
  • Re-use & Attribution / Privacy
  • Harmful Language Statement
  • Support the Libraries
Duke University