TitleAltered steady state and activity-dependent de novo protein expression in fragile X syndrome.
Publication TypeJournal Article
Year of Publication2019
AuthorsBowling H, Bhattacharya A, Zhang G, Alam D, Lebowitz JZ, Bohm-Levine N, Lin D, Singha P, Mamcarz M, Puckett R, Zhou L, Aryal S, Sharp K, Kirshenbaum K, Berry-Kravis E, Neubert TA, Klann E
JournalNat Commun
Date Published2019 Apr 12

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.

Alternate JournalNat Commun
PubMed ID30979884
PubMed Central IDPMC6461708
Grant ListR01 NS034007 / NS / NINDS NIH HHS / United States
R37 NS034007 / NS / NINDS NIH HHS / United States
P30 NS050276 / NS / NINDS NIH HHS / United States
U54 HD082013 / HD / NICHD NIH HHS / United States
R29 NS034007 / NS / NINDS NIH HHS / United States
S10 RR027990 / RR / NCRR NIH HHS / United States