Altered steady state and activity-dependent de novo protein expression in fragile X syndrome.
Heather BowlingAditi BhattacharyaGuoan ZhangDanyal AlamJoseph Z LebowitzNathaniel Bohm-LevineDerek LinPriyangvada SinghaMaggie MamcarzRosemary PuckettLili ZhouSameer AryalKevin SharpKent KirshenbaumElizabeth Berry-KravisThomas A NeubertEric KlannPublished in: Nature communications (2019)
Whether fragile X mental retardation protein (FMRP) target mRNAs and neuronal activity contributing to elevated basal neuronal protein synthesis in fragile X syndrome (FXS) is unclear. Our proteomic experiments reveal that the de novo translational profile in FXS model mice is altered at steady state and in response to metabotropic glutamate receptor (mGluR) stimulation, but the proteins expressed differ under these conditions. Several altered proteins, including Hexokinase 1 and Ras, also are expressed in the blood of FXS model mice and pharmacological treatments previously reported to ameliorate phenotypes modify their abundance in blood. In addition, plasma levels of Hexokinase 1 and Ras differ between FXS patients and healthy volunteers. Our data suggest that brain-based de novo proteomics in FXS model mice can be used to find altered expression of proteins in blood that could serve as disease-state biomarkers in individuals with FXS.
Keyphrases
- wild type
- high fat diet induced
- end stage renal disease
- newly diagnosed
- chronic kidney disease
- mass spectrometry
- cerebral ischemia
- mental health
- prognostic factors
- gene expression
- machine learning
- insulin resistance
- dna methylation
- label free
- metabolic syndrome
- patient reported outcomes
- big data
- blood brain barrier
- amino acid
- deep learning
- long non coding rna
- subarachnoid hemorrhage
- anaerobic digestion