FMRP(1–297)-tat restores ion channel and synaptic function in a model of Fragile X syndrome

Author:

Zhan Xiaoqin,Asmara Hadhimulya,Cheng NingORCID,Sahu Giriraj,Sanchez Eduardo,Zhang Fang-Xiong,Zamponi Gerald W.ORCID,Rho Jong M.,Turner Ray W.ORCID

Abstract

AbstractFragile X Syndrome results from a loss of Fragile X Mental Retardation Protein (FMRP). We now show that FMRP is a member of a Cav3-Kv4 ion channel complex that is known to regulate A-type potassium current in cerebellar granule cells to produce mossy fiber LTP. Mossy fiber LTP is absent in Fmr1 knockout (KO) mice but is restored by FMRP(1-297)-tat peptide. This peptide further rapidly permeates the blood-brain barrier to enter cells across the cerebellar-cortical axis that restores the balance of protein translation for at least 24 h and transiently reduces elevated levels of activity of adult Fmr1 KO mice in the Open Field Test. These data reveal that FMRP(1-297)-tat can improve function from the levels of protein translation to synaptic efficacy and behaviour in a model of Fragile X syndrome, identifying a potential therapeutic strategy for this genetic disorder.

Funder

FRAXA Research Foundation

Gouvernement du Canada | Instituts de Recherche en Santé du Canada | CIHR Skin Research Training Centre

SFARI Explorer Grant Fragile X Canada Postdoctoral Fellowship Hotchkiss Brain Institute / Cumming School of Medicine PDF

Publisher

Springer Science and Business Media LLC

Subject

General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry

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