title: Neuroprotective and memory enhancing properties of a dual agonist of the FGF receptor and NCAM.
abstract: The fibroblast growth factor receptor (FGFR) plays a vital role in the development of the nervous system regulating a multitude of cellular processes. One of the interaction partners of the FGFR is the neural cell adhesion molecule (NCAM), which is known to play an important role in neuronal development, regeneration and synaptic plasticity. Thus, simultaneous activation of FGFR- and NCAM-mediated signaling pathways may be expected to affect processes underlying neurodegenerative diseases. We here report the identification of a peptide compound, Enreptin, capable of interacting with both FGFR and NCAM. We demonstrate that this dual specificity agonist induces phosphorylation of FGFR and differentiation and survival of primary neurons in vitro, and that these effects are inhibited by abrogation of both NCAM and FGFR signaling pathways. Furthermore, Enreptin crosses the blood-brain barrier after subcutaneous administration, enhances long-term memory in normal mice and ameliorates memory deficit in mice with induced brain inflammation. Moreover, Enreptin reduces cognitive impairment and neuronal death induced by Aβ25-35 in a rat model of Alzheimer's disease, and reduces the mortality rate and clinical signs of experimental autoimmune encephalomyelitis in rats. Thus, Enreptin is an attractive candidate for the treatment of neurological diseases.
authors: Protein Laboratory, Department of Neuroscience and Pharmacology, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.
authors: Maj N
authors: MN
authors: Enevoldsen
authors: Artur
authors: A
authors: Kochoyan
authors: Monika
authors: M
authors: Jurgenson
authors: Külli
authors: K
authors: Jaako
authors: Oksana
authors: O
authors: Dmytriyeva
authors: Peter S
authors: PS
authors: Walmod
authors: Jesper D
authors: JD
authors: Nielsen
authors: Janne
authors: J
authors: Nielsen
authors: Shizhong
authors: S
authors: Li
authors: Irina
authors: I
authors: Korshunova
authors: Boris
authors: B
authors: Klementiev
authors: Tatiana
authors: T
authors: Novikova
authors: Alexander
authors: A
authors: Zharkovsky
authors: Vladimir
authors: V
authors: Berezin
authors: Elisabeth
authors: E
authors: Bock
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001927:Brain Diseases / Q000473:pathology; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D003072:Cognition Disorders / Q000473:pathology; D004195:Disease Models, Animal; D006801:Humans; D008297:Male; D008568:Memory / Q000187:drug effects*; D051379:Mice; D008807:Mice, Inbred BALB C; D019006:Neural Cell Adhesion Molecules / Q000819:agonists*; D009474:Neurons / Q000166:cytology / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009842:Oligopeptides / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D017468:Receptors, Fibroblast Growth Factor / Q000819:agonists*; D020349:Surface Plasmon Resonance
chemical_list: D019006:Neural Cell Adhesion Molecules; D018696:Neuroprotective Agents; D009842:Oligopeptides; D017468:Receptors, Fibroblast Growth Factor; C580750:alanyl-lysyl-threonyl-valyl-lysyl-phenylalanyl-lysine