title: ApolipoproteinE mimetic peptides improve outcome after focal ischemia.
abstract: Growing clinical evidence implicates isoform-specific effects of apolipoprotein E (apoE) in reducing neuroinflammation and mediating adaptive responses following ischemic and traumatic brain injury. However, the intact apoE holoprotein does not cross the blood-brain barrier and thus has limited therapeutic potential. We have created a small peptide, COG1410 (acetyl-AS-Aib-LRKL-Aib-KRLL-amide), derived from the apoE receptor-binding region. COG1410 retains the anti-inflammatory and neuroprotective biological properties of the intact holoprotein and penetrates the blood-brain barrier. In the current study, we utilized a murine model of transient focal cerebral ischemia and reperfusion to demonstrate that intravenous (IV) administration of COG1410 reduces infarct volume and radiographic progression of infarct, and improves functional outcome as assessed by rotarod when delivered up to 4h after ischemia onset.
authors.affiliation: Department of Medicine (Neurology), Duke University School of Medicine, Durham, NC 27710, USA.
authors.forename: Haichen
authors.initials: H
authors.lastname: Wang
authors.forename: Lauren G
authors.initials: LG
authors.lastname: Anderson
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Lascola
authors.forename: Michael L
authors.initials: ML
authors.lastname: James
authors.forename: Talaignair N
authors.initials: TN
authors.lastname: Venkatraman
authors.forename: Ellen R
authors.initials: ER
authors.lastname: Bennett
authors.forename: Shawn K
authors.initials: SK
authors.lastname: Acheson
authors.forename: Michael P
authors.initials: MP
authors.lastname: Vitek
authors.forename: Daniel T
authors.initials: DT
authors.lastname: Laskowitz
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001057:Apolipoproteins E / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use; D001929:Brain Edema / Q000209:etiology / Q000517:prevention & control; D020520:Brain Infarction / Q000209:etiology / Q000517:prevention & control; D002853:Chromatography, Liquid; D004195:Disease Models, Animal; D004660:Encephalitis / Q000209:etiology / Q000517:prevention & control; D007839:Functional Laterality / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D020244:Infarction, Middle Cerebral Artery / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D008279:Magnetic Resonance Imaging; D008297:Male; D013058:Mass Spectrometry; D051379:Mice; D008810:Mice, Inbred C57BL; D009069:Movement Disorders / Q000188:drug therapy / Q000209:etiology; D012333:RNA, Messenger / Q000378:metabolism; D020127:Recovery of Function / Q000187:drug effects*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D001057:Apolipoproteins E; C524548:COG1410; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha