Functional peptide sequences derived from extracellular matrix glycoproteins and their receptors: strategies to improve neuronal regeneration.
Peptides derived from extracellular matrix proteins have the potential to function as potent therapeutic reagents to increase neuronal regeneration following central nervous system (CNS) injury, yet their efficacy as pharmaceutical reagents is dependent upon the expression of cognate receptors in the target tissue. This type of codependency is clearly observed in successful models of axonal regeneration in the peripheral nervous system, but not in the normally nonregenerating adult CNS. Successful regeneration is most closely correlated with the induction of integrins on the surface of peripheral neurons. This suggests that in order to achieve optimal neurite regrowth in the injured adult CNS, therapeutic strategies must include approaches that increase the number of integrins and other key receptors in damaged central neurons, as well as provide the appropriate growth-promoting peptides in a "regeneration cocktail." In this review, we describe the ability of peptides derived from tenascin- C, fibronectin, and laminin-1 to influence neuronal growth. In addition, we also discuss the implications of peptide/receptor interactions for strategies to improve neuronal regeneration.
Meiners
Sally
S
Department of Pharmacology, UMDNJ-Robert Wood Johnson Medical School, 675 Hoes Lane, Piscataway, New Jersey, 08854 USA. meiners@umdnj.edu
Mercado
Mary Lynn T
ML
D000818:Animals; D001930:Brain Injuries / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D002490:Central Nervous System / Q000254:growth & development* / Q000293:injuries / Q000378:metabolism*; D016326:Extracellular Matrix Proteins / Q000378:metabolism* / Q000494:pharmacology / Q000627:therapeutic use; D020439:Growth Cones / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D009414:Nerve Growth Factors / Q000302:isolation & purification / Q000494:pharmacology; D009416:Nerve Regeneration / Q000187:drug effects / Q000502:physiology*; D011956:Receptors, Cell Surface / Q000378:metabolism / Q000627:therapeutic use
D016326:Extracellular Matrix Proteins; D009414:Nerve Growth Factors; D011956:Receptors, Cell Surface