NCAM mimetic peptides: Pharmacological and therapeutic potential.
The neural cell adhesion molecule (NCAM) plays an important role in neuronal differentiation and synaptic plasticity, making it an attractive target for the development of drugs for the treatment of neurodegenerative disorders. NCAM binds to itself (homophilic binding) and to a series of counter-receptors, including the fibroblast growth factor receptor (FGFR), other adhesion molecules, and various extracellular matrix components (heterophilic binding). By means of combinatorial chemistry and based on the unraveling of the structure of NCAM, it has been possible to develop a number of peptides that mimic NCAM homophilic binding. These peptides interfere with cell adhesion and promote differentiation and cell survival. Recently, a peptide mimicking the heterophilic binding to FGFR has also been identified. It binds and activates the receptor, thereby modulating neurite extension and synaptic plasticity.
Berezin
Vladimir
V
Protein Laboratory, Institute of Molecular Pathology, University of Copenhagen, Panum Institute 6.2, Blegdamsvej 3, DK-2200 Copenhagen N., Denmark. berezin@plab.ku.dk
Bock
Elisabeth
E
D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects* / Q000502:physiology; D002454:Cell Differentiation / Q000187:drug effects* / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D006801:Humans; D019006:Neural Cell Adhesion Molecules / Q000819:agonists* / Q000737:chemistry; D019636:Neurodegenerative Diseases / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D009473:Neuronal Plasticity / Q000187:drug effects* / Q000502:physiology; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D011485:Protein Binding / Q000187:drug effects / Q000502:physiology; D017468:Receptors, Fibroblast Growth Factor / Q000187:drug effects / Q000378:metabolism
D019006:Neural Cell Adhesion Molecules; D010455:Peptides; D017468:Receptors, Fibroblast Growth Factor