FMRP(1–297)-tat restores ion channel and synaptic function in a model of Fragile X syndrome
Fragile 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 knoc...
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Published in | Nature communications Vol. 11; no. 1; p. 2755 |
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Main Authors | , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
London
Nature Publishing Group UK
02.06.2020
Nature Publishing Group Nature Portfolio |
Subjects | |
Online Access | Get full text |
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Summary: | Fragile 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.
Fragile X Mental Retardation Protein regulates synaptic plasticity and its loss results in Fragile X Syndrome. Here, the authors show that the FMRP(1-297)-
tat
peptide can permeate the BBB, restore protein translation and mossy fiber LTP, and reduce elevated levels of activity in
Fmr1
KO mice. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 2041-1723 2041-1723 |
DOI: | 10.1038/s41467-020-16250-4 |