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Early‐phase ERK activation as a biomarker for metabolic status in fragile X syndrome
Author(s) -
Weng Ning,
Weiler Ivan Jeanne,
Sumis Allison,
BerryKravis Elizabeth,
Greenough William T.
Publication year - 2008
Publication title -
american journal of medical genetics part b: neuropsychiatric genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.393
H-Index - 126
eISSN - 1552-485X
pISSN - 1552-4841
DOI - 10.1002/ajmg.b.30765
Subject(s) - fragile x syndrome , biomarker , kinase , mapk/erk pathway , extracellular , biology , microbiology and biotechnology , neuroscience , protein kinase a , signal transduction , medicine , endocrinology , genetics
Lack of production of the Fragile X Mental Retardation Protein (FMRP) leads to changes in dendritic morphology and resultant cognitive and behavioral manifestations characteristic of individuals with Fragile X syndrome (FXS). FMRP is an RNA‐binding protein that is believed to regulate the translation of a large number (probably over 100) of other proteins, leading to a complex and variable set of symptoms in FXS. In a mouse model of FXS, we previously observed delayed initiation of synaptically localized protein synthesis in response to neurotransmitter stimulation, as compared to wild‐type mice. We now likewise have observed delayed early‐phase phosphorylation of extracellular‐signal regulated kinase (ERK), a nodal point for cell signaling cascades, in both neurons and thymocytes of fmr‐1 KO mice. We further report that early‐phase kinetics of ERK activation in lymphocytes from human peripheral blood is delayed in a cohort of individuals with FXS, relative to normlal controls, suggesting a potential biomarker to measure metabolic status of disease for individuals with FXS. © 2008 Wiley‐Liss, Inc.