NCAM and FGF

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NCAM and FGL have demonstrated evidence of being relevant in neurodegeneration including Alzheimer's disease (e.g. the latest PNAS publication "FGF2 gene transfer restores hippocampal functions in mouse models of Alzheimer's disease and has therapeutic implications for neurocognitive disorders").

Prof Elisabeth Bock from the University of Copenhagen has, through her pioneering work over more than three decades, made a major contribution to the understanding of the Neural Cell Adhesion Molecule (NCAM). This work, on which Enkam is based, has significantly advanced the understanding of cell adhesion. The FGL peptides are identical to the human NCAM and mimic NCAM's regulatory role over the Fibroblast Growth Factor Receptor (FGFR).

CAMs are known to play a significant role in the development of tissues and organs. In recent years, increasing evidence of a direct regulatory role of CAMs over growth factors has been published. NCAM is expressed in the nervous system, as well as in selected tissues outside the brain (e.g. muscle cells).

Furthermore, NCAM-derived peptides which target one of its ligands (e.g. the FGF-receptor) can mimic NCAM's unique modulatory activity. This extends their scope and potential application. This complex and valuable group of targets has been made accessible by dissecting the 3D structure of complex interactions between receptors and their ligands, through a previous EU funded project (PROMEMORIA).

 

Literature

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Reviews

Berezin et al: NCAM mimetic peptides: Pharmacological and therapeutic potential. J Mol Neurosci 2004;22:33-39.

Ezzat S et al: The molecular pathogenetic role of cell adhesion in endocrine neoplasia. J Clin Pathol 2005;58:1121-1125.

Grose R et al: Fibroblast growth factor signaling in tumorigenesis. Cytokine Growth Factor Rev 2005;16:179-186.

Sandi C: Stress, cognitive impairment and cell adhesion molecules. Nat Rev Neurosci 2004;5:917-930.

Walmod PS et al: Zippers make signals: NCAM-mediated molecular interactions and signal transduction. Neurochem Res 2004;29:2015-2035.

 

FGL specific literature

Anand R et al: Tolerability, safety and pharmacokinetics of the FGLL peptide, a novel mimetic of neural cell adhesion molecule, following intranasal administration in healthy volunteers. Clin Pharmacokin 2007;46:351-358.

Cambon K et al: A synthetic neural cell adhesion molecule mimetic peptide promotes synaptogenesis, enhances presynaptic function, and facilitates memory consolidation. J Neurosci 2004;24:4197-4204.

Kiselyov VV et al: Structural basis for a direct interaction between FGFR1 and NCAM and evidence for a regulatory role of ATP. Structure 2003;11:691-701.

Kiyota et al.: FGF2 gene transfer restores hippocampal functions in mouse models of Alzheimer's disease and has therapeutic implications for neurocognitive disorders. PNAS 2011 (e-publication)

Klementiev B et al.: A neural cell adhesion molecule-derived peptide reduces neuropathological signs and cognitive impairment induced by A-beta25-35. Neuroscience 2007;145:209-224.

Neiiendam JL et al: An NCAM-derived FGF-receptor agonist, the FGL-peptide, induces neurite outgrowth and neuronal survival in primary rat neurons. J Neurochem 2004;91:920-935.

Secher T et al: A neural cell adhesion molecule-derived fibroblast growth factor receptor agonist, the FGL-peptide, promotes early postnatal sensorimotor development and enhances social memory retention. Neuroscience 2006;141:1289-1299.

Skibo GG et al: A synthetic NCAM-derived peptide, FGL, protects hippocampal neurons from ischemic insult both in vitro and in vivo. Eur J Neurosci 2005;22:1589-1596.