Age-dependent attenuation of spatial memory deficits by the histone acetyltransferase p300/CBP-associated factor (PCAF) in 3xTG Alzheimer's disease mice

Histone acetylation, catalyzed by histone acetyltransferases, has emerged as a promising therapeutic strategy in Alzheimer's disease (AD). By longitudinally characterizing spatial memory at 3, 6, and 9 mo of age, we show that acute activation and inhibition of the histone acetyltransferase PCAF...

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Detalles Bibliográficos
Autores principales: Creighton, Samantha D., Jardine, Kristen H., Desimone, Alexa, Zmetana, Megan, Castellano, Sabrina, Milite, Ciro, Sbardella, Gianluca, Winters, Boyer D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory Press 2022
Materias:
Brief Communication
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8852226/
https://www.ncbi.nlm.nih.gov/pubmed/35169045
http://dx.doi.org/10.1101/lm.053536.121
Descripción
Sumario:Histone acetylation, catalyzed by histone acetyltransferases, has emerged as a promising therapeutic strategy in Alzheimer's disease (AD). By longitudinally characterizing spatial memory at 3, 6, and 9 mo of age, we show that acute activation and inhibition of the histone acetyltransferase PCAF remediated memory impairments in 3xTG-AD mice in an age-related bidirectional manner. At 3 and 6 mo of age, PCAF activation ameliorated memory deficits. At 9 mo of age, PCAF activation had no effect on spatial memory, whereas PCAF inhibition improved memory deficits in females. This work reveals a complex potential therapeutic role for PCAF in AD, initially benefitting memory but becoming detrimental as the disease progresses.

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