Early-phase ERK activation as a biomarker for metabolic status in fragile X syndrome.
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.
Weng
Ning
N
Beckman Institute, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA.
Weiler
Ivan Jeanne
IJ
Sumis
Allison
A
Berry-Kravis
Elizabeth
E
Greenough
William T
WT
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics; D005600:Fragile X Syndrome / Q000378:metabolism*; D006801:Humans; D008214:Lymphocytes / Q000378:metabolism / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation; D013950:Thymus Gland / Q000378:metabolism / Q000473:pathology; D013997:Time Factors
D015415:Biomarkers; D048049:Extracellular Signal-Regulated MAP Kinases; D051860:Fragile X Messenger Ribonucleoprotein 1