| First Author | Zhan X | Year | 2020 |
| Journal | Nat Commun | Volume | 11 |
| Issue | 1 | Pages | 2755 |
| PubMed ID | 32488011 | Mgi Jnum | J:292212 |
| Mgi Id | MGI:6447598 | Doi | 10.1038/s41467-020-16250-4 |
| Citation | Zhan X, et al. (2020) FMRP(1-297)-tat restores ion channel and synaptic function in a model of Fragile X syndrome. Nat Commun 11(1):2755 |
| abstractText | 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. |
