An MD2-perturbing peptide has therapeutic effects in rodent and rhesus monkey models of stroke.

Science Translational Medicine
Zongping FangLize Xiong

Abstract

Studies have failed to translate more than 1000 experimental treatments from bench to bedside, leaving stroke as the second leading cause of death in the world. Thrombolysis within 4.5 hours is the recommended therapy for stroke and cannot be performed until neuroimaging is used to distinguish ischemic stroke from hemorrhagic stroke. Therefore, finding a common and critical therapeutic target for both ischemic and hemorrhagic stroke is appealing. Here, we report that the expression of myeloid differentiation protein 2 (MD2), which is traditionally regarded to be expressed only in microglia in the normal brain, was markedly increased in cortical neurons after stroke. We synthesized a small peptide, Trans-trans-activating (Tat)-cold-inducible RNA binding protein (Tat-CIRP), which perturbed the function of MD2 and strongly protected neurons against excitotoxic injury in vitro. In addition, systemic administration of Tat-CIRP or genetic deletion of MD2 induced robust neuroprotection against ischemic and hemorrhagic stroke in mice. Tat-CIRP reduced the brain infarct volume and preserved neurological function in rhesus monkeys 30 days after ischemic stroke. Tat-CIRP efficiently crossed the blood-brain barrier and showed a wide therap...Continue Reading

References

Jun 9, 1997·FEBS Letters·T IshidateT Akiyama
Oct 2, 1998·Stroke; a Journal of Cerebral Circulation·W ClarkK Hazel
Sep 1, 1999·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·M M AartsJ E Henderson
Jun 11, 2002·Nature Immunology·Yoshinori NagaiKensuke Miyake
Dec 13, 2002·Nature·Nathalie MatterHarald König
Jun 26, 2003·Proceedings of the National Academy of Sciences of the United States of America·Seija LehnardtTimothy Vartanian
Jul 28, 2004·Trends in Biochemical Sciences·Monique Gangloff, Nicholas J Gay
Jan 13, 2006·Nature Chemical Biology·Alexei DegterevJunying Yuan
Jun 3, 2006·Science·Séverine BoilléeDon W Cleveland
Aug 22, 2006·Immunobiology·Alberto VisintinDouglas T Golenbock
Oct 19, 2007·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Shannon Reagan-ShawNihal Ahmad
May 31, 2011·Molecular Cell·Parameswaran Ramakrishnan, David Baltimore
Jul 7, 2011·Circulation·Anthony S Kim, S Claiborne Johnston
Dec 27, 2011·Cell·Takatoshi IijimaPeter Scheiffele
Jun 8, 2012·Nature Medicine·Lidia Garcia-Bonilla, Costantino Iadecola
Sep 18, 2012·Stroke; a Journal of Cerebral Circulation·Yu GanGuodong Cao
Feb 8, 2013·The New England Journal of Medicine·Alfonso CicconeUNKNOWN SYNTHESIS Expansion Investigators
May 3, 2013·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Shu ZhangYu Tian Wang
Jul 11, 2013·Stroke; a Journal of Cerebral Circulation·Yan-Chun WangQing-Wu Yang
Jan 31, 2014·The New England Journal of Medicine·Andreas Linkermann, Douglas R Green
Jun 5, 2014·Frontiers in Bioscience (Landmark Edition)·Guangjie DuanYousheng Liu
Aug 28, 2014·CNS Drugs·Kiyoshi KikuchiSalunya Tancharoen
Jan 17, 2015·Nature·Manolis Pasparakis, Peter Vandenabeele
Mar 6, 2015·Nature Protocols·Li ZhangZheng Gang Zhang
Apr 18, 2015·The New England Journal of Medicine·Anthony J Furlan
Apr 18, 2015·The New England Journal of Medicine·Tudor G JovinUNKNOWN REVASCAT Trial Investigators
Jan 14, 2016·Nature Communications·Mikael FeracciCyril Dominguez
Mar 9, 2017·Alcoholism, Clinical and Experimental Research·Colleen J Lawrimore, Fulton T Crews
Nov 10, 2017·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Di WuXunming Ji

❮ Previous
Next ❯

Citations

Jul 10, 2021·Nature Reviews. Drug Discovery·M Teresa Villanueva

❮ Previous
Next ❯

Related Concepts

Related Feeds

Brain Ischemia

Brain ischemia is a condition in which there is insufficient blood flow to the brain to meet metabolic demand. Discover the latest research on brain ischemia here.

Blood Brain Barrier Chips

The blood brain barrier (BBB) is comprised of endothelial cells that regulate the influx and outflux of plasma concentrations. Lab-on-a-chip devices allow scientists to model diseases and mechanisms such as the passage of therapeutic antibodies across the BBB. Discover the latest research on BBB chips here.

Barrel cortex

Here is the latest research on barrel cortex, a region of somatosensory and motor corticies in the brain, which are used by animals that rely on whiskers for world exploration.

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis

Acute Stroke

A stroke occurs when blood supply to the brain is interrupted depriving the brain of oxygen and nutrients. This feed focuses cerebrovascular accidents including ischemic and paralytic stroke.

Blood Brain Barrier

The blood brain barrier is a border that separates blood from cerebrospinal fluid. Discover the latest search on this highly selective semipermeable membrane here.