FMRP(1-297)-tat restores ion channel and synaptic function in a model of Fragile X syndrome.
Nat Commun
; 11(1): 2755, 2020 06 02.
Article
en En
| MEDLINE
| ID: mdl-32488011
ABSTRACT
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.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Proteína de la Discapacidad Intelectual del Síndrome del Cromosoma X Frágil
/
Síndrome del Cromosoma X Frágil
/
Canales Iónicos
Límite:
Animals
Idioma:
En
Revista:
Nat Commun
Asunto de la revista:
BIOLOGIA
/
CIENCIA
Año:
2020
Tipo del documento:
Article
País de afiliación:
Canadá