The NCAM-derived P2 peptide facilitates recovery of cognitive and motor function and ameliorates neuropathology following traumatic brain injury.
The neural cell adhesion molecule (NCAM) plays a crucial role during development and regeneration of the nervous system, mediating neuronal differentiation, survival and plasticity. Moreover, NCAM regulates learning and memory. A peptide termed P2, corresponding to a 12-amino-acid sequence in the second immunoglobulin (Ig)-like module of NCAM, represents the natural cis-binding site for the first NCAM Ig module. The P2 peptide targets NCAM, thereby inducing a number of intracellular signaling events leading to the stimulation of neurite outgrowth and promotion of neuronal survival in vitro. The present study evaluated the effect of the P2 peptide on functional and histological outcomes following traumatic brain injury inflicted by a cortical cryogenic lesion. Lesioned rats were injected subcutaneously with P2 peptide, 5 mg/kg daily for 15 days beginning 2 h after injury. This treatment significantly improved postlesion recovery of motor and cognitive function, reduced neuronal degeneration, protected cells against oxidative stress, and increased reactive astrogliosis and neuronal plasticity in the sublesional area. P2 appeared rapidly in blood and cerebrospinal fluid after subcutaneous administration and remained detectable in blood for up to 5 h. The results suggest that P2 has therapeutic potential for the treatment of traumatic brain injury.
ENKAM Pharmaceuticals A/S; Department of Neuroscience and Pharmacology, School of Medicine, University of Copenhagen, Copenhagen, Denmark. klement@plab.ku.dk
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Klementiev
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Novikova
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Korshunova
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Berezin
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Bock
D000818:Animals; D001665:Binding Sites / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D001930:Brain Injuries / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D002454:Cell Differentiation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003072:Cognition Disorders / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D005911:Gliosis / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology; D008297:Male; D009069:Movement Disorders / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology; D009185:Myelin Proteins / Q000493:pharmacokinetics* / Q000627:therapeutic use; D009410:Nerve Degeneration / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology; D019006:Neural Cell Adhesion Molecules / Q000378:metabolism*; D009473:Neuronal Plasticity / Q000187:drug effects; D018696:Neuroprotective Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D011485:Protein Binding / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D020127:Recovery of Function / Q000187:drug effects*; D016896:Treatment Outcome
D009185:Myelin Proteins; D019006:Neural Cell Adhesion Molecules; D018696:Neuroprotective Agents; C425263:P2 peptide