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221 Low levels of nerve growth factor (NGF) in CSF of children with rett syndrome
Author(s) -
Riikonen R.,
Vanhala R.,
Lindholm D.
Publication year - 1996
Publication title -
international journal of developmental neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.761
H-Index - 88
eISSN - 1873-474X
pISSN - 0736-5748
DOI - 10.1016/0736-5748(96)80410-2
Subject(s) - rett syndrome , citation , nerve growth factor , impact factor , library science , psychology , medicine , computer science , political science , biology , genetics , law , receptor , gene
Despite the large sequence similarity (60 %) among the known neurotrophins within the NGF family, they display different activities on different subset of neurons. Recent studies have shown that the various neurotrophins are ligands with high affmity to different receptors of the Trk family of tyrosine kinase receptors. In earlier studies we have defined five NGF-amino-acid residues giving NT-3 NGF-like activity. The most efficient NGFlike transformation was obtained by the exchange of Pro-Val and Leu-Val-Gly in NT-3 to the NGF residues Val-Phe and Gin-AlaAla. The mutated sites are situated in two b-loops at one end of the NGF molecule, forming a cleft that could specifically interact with high affmity to the signalling NGF receptor complex. The other site, situated in the N-terminal of NGF, consists of a one amino acid replacement, from a Lys to a Pro and an extra residue, a Phe inserted into the corresponding position. The mutants were characterised by measuring surival of chick sympathetic neurons, tibre outgrowth from chick sympathetic ganglia and activation of the human TrkA receptor. Based on these data a study with potential low molecular agonists/antagonists was undertaken. 220