Neuroprotection by cell permeable TAT-mGluR1 peptide in ischemia: Synergy between carrier and cargo sequences

Wei Xu, Miou Zhou, Michel Baudry

Research output: Contribution to journalReview article

24 Citations (Scopus)

Abstract

Overactivation of glutamate receptors is a critical mechanism for neuronal death in ischemic stroke. Previously, we reported that overactivation of N-methyl-D-aspartate (NMDA)-type glutamate receptor induced calpain-mediated truncation of metabotropic glutamate receptor mGluR1α, resulting in suppression of its neuroprotective signaling pathway. A fusion peptide containing the transactivating regulatory protein (TAT) protein transduction domain (PTD) and the mGluR1α sequence spanning the calpain cleavage site effectively blocked mGluR1α truncation and protected neurons against NMDA-induced neuronal toxicity. We recently evaluated the role of this mechanism in ischemia-induced cell death. We found that mGluR1α was truncated in both in vitro and in vivo models of stroke and that this truncation was accompanied by the typical calpain-mediated proteolysis of spectrin. The TAT-mGluR1 fusion peptide produced robust neuroprotective effect in the in vitro model of stroke. In addition, we found that the TAT protein transduction domain peptide itself altered the function of membrane channels through some unknown mechanisms and showed some mild neuroprotective effects. Together, these experiments indicated a synergistic relationship between the TAT carrier sequence and the mGluR1α peptide cargo sequence, and this synergy might account for the neuroprotective properties of the TAT-mGluR1 peptide.

Original languageEnglish (US)
Pages (from-to)409-414
Number of pages6
JournalNeuroscientist
Volume14
Issue number5
DOIs
StatePublished - Oct 1 2008

Fingerprint

Ischemia
Calpain
Stroke
Glutamate Receptors
Neuroprotective Agents
Peptides
Spectrin
Metabotropic Glutamate Receptors
N-Methylaspartate
N-Methyl-D-Aspartate Receptors
Ion Channels
Proteolysis
Cell Death
metabotropic glutamate receptor type 1
TAT-mGluR1 peptide
Neuroprotection
Neurons
Proteins
In Vitro Techniques
Protein Domains

Keywords

  • Calpain
  • Metabotropic glutamate receptor
  • Neuroprotection
  • NMDA receptor
  • Stroke

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Neurology

Cite this

Neuroprotection by cell permeable TAT-mGluR1 peptide in ischemia : Synergy between carrier and cargo sequences. / Xu, Wei; Zhou, Miou; Baudry, Michel.

In: Neuroscientist, Vol. 14, No. 5, 01.10.2008, p. 409-414.

Research output: Contribution to journalReview article

@article{29883c9bdfa44841a399ae0ba06f794c,
title = "Neuroprotection by cell permeable TAT-mGluR1 peptide in ischemia: Synergy between carrier and cargo sequences",
abstract = "Overactivation of glutamate receptors is a critical mechanism for neuronal death in ischemic stroke. Previously, we reported that overactivation of N-methyl-D-aspartate (NMDA)-type glutamate receptor induced calpain-mediated truncation of metabotropic glutamate receptor mGluR1α, resulting in suppression of its neuroprotective signaling pathway. A fusion peptide containing the transactivating regulatory protein (TAT) protein transduction domain (PTD) and the mGluR1α sequence spanning the calpain cleavage site effectively blocked mGluR1α truncation and protected neurons against NMDA-induced neuronal toxicity. We recently evaluated the role of this mechanism in ischemia-induced cell death. We found that mGluR1α was truncated in both in vitro and in vivo models of stroke and that this truncation was accompanied by the typical calpain-mediated proteolysis of spectrin. The TAT-mGluR1 fusion peptide produced robust neuroprotective effect in the in vitro model of stroke. In addition, we found that the TAT protein transduction domain peptide itself altered the function of membrane channels through some unknown mechanisms and showed some mild neuroprotective effects. Together, these experiments indicated a synergistic relationship between the TAT carrier sequence and the mGluR1α peptide cargo sequence, and this synergy might account for the neuroprotective properties of the TAT-mGluR1 peptide.",
keywords = "Calpain, Metabotropic glutamate receptor, Neuroprotection, NMDA receptor, Stroke",
author = "Wei Xu and Miou Zhou and Michel Baudry",
year = "2008",
month = "10",
day = "1",
doi = "10.1177/1073858407309762",
language = "English (US)",
volume = "14",
pages = "409--414",
journal = "Neuroscientist",
issn = "1073-8584",
publisher = "SAGE Publications Inc.",
number = "5",

}

TY - JOUR

T1 - Neuroprotection by cell permeable TAT-mGluR1 peptide in ischemia

T2 - Synergy between carrier and cargo sequences

AU - Xu, Wei

AU - Zhou, Miou

AU - Baudry, Michel

PY - 2008/10/1

Y1 - 2008/10/1

N2 - Overactivation of glutamate receptors is a critical mechanism for neuronal death in ischemic stroke. Previously, we reported that overactivation of N-methyl-D-aspartate (NMDA)-type glutamate receptor induced calpain-mediated truncation of metabotropic glutamate receptor mGluR1α, resulting in suppression of its neuroprotective signaling pathway. A fusion peptide containing the transactivating regulatory protein (TAT) protein transduction domain (PTD) and the mGluR1α sequence spanning the calpain cleavage site effectively blocked mGluR1α truncation and protected neurons against NMDA-induced neuronal toxicity. We recently evaluated the role of this mechanism in ischemia-induced cell death. We found that mGluR1α was truncated in both in vitro and in vivo models of stroke and that this truncation was accompanied by the typical calpain-mediated proteolysis of spectrin. The TAT-mGluR1 fusion peptide produced robust neuroprotective effect in the in vitro model of stroke. In addition, we found that the TAT protein transduction domain peptide itself altered the function of membrane channels through some unknown mechanisms and showed some mild neuroprotective effects. Together, these experiments indicated a synergistic relationship between the TAT carrier sequence and the mGluR1α peptide cargo sequence, and this synergy might account for the neuroprotective properties of the TAT-mGluR1 peptide.

AB - Overactivation of glutamate receptors is a critical mechanism for neuronal death in ischemic stroke. Previously, we reported that overactivation of N-methyl-D-aspartate (NMDA)-type glutamate receptor induced calpain-mediated truncation of metabotropic glutamate receptor mGluR1α, resulting in suppression of its neuroprotective signaling pathway. A fusion peptide containing the transactivating regulatory protein (TAT) protein transduction domain (PTD) and the mGluR1α sequence spanning the calpain cleavage site effectively blocked mGluR1α truncation and protected neurons against NMDA-induced neuronal toxicity. We recently evaluated the role of this mechanism in ischemia-induced cell death. We found that mGluR1α was truncated in both in vitro and in vivo models of stroke and that this truncation was accompanied by the typical calpain-mediated proteolysis of spectrin. The TAT-mGluR1 fusion peptide produced robust neuroprotective effect in the in vitro model of stroke. In addition, we found that the TAT protein transduction domain peptide itself altered the function of membrane channels through some unknown mechanisms and showed some mild neuroprotective effects. Together, these experiments indicated a synergistic relationship between the TAT carrier sequence and the mGluR1α peptide cargo sequence, and this synergy might account for the neuroprotective properties of the TAT-mGluR1 peptide.

KW - Calpain

KW - Metabotropic glutamate receptor

KW - Neuroprotection

KW - NMDA receptor

KW - Stroke

UR - http://www.scopus.com/inward/record.url?scp=52449134307&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=52449134307&partnerID=8YFLogxK

U2 - 10.1177/1073858407309762

DO - 10.1177/1073858407309762

M3 - Review article

C2 - 18000067

AN - SCOPUS:52449134307

VL - 14

SP - 409

EP - 414

JO - Neuroscientist

JF - Neuroscientist

SN - 1073-8584

IS - 5

ER -