Progranulin (GRN) haploinsufficiency is a frequent cause of familial frontotemporal
dementia, a currently untreatable progressive neurodegenerative disease. By chemical
library screening, we identified suberoylanilide hydroxamic acid (SAHA), a Food and Drug
Administration-approved histone deacetylase inhibitor, as an enhancer of GRN expression.
SAHA dose-dependently increased GRN mRNA and protein levels in cultured cells and
restored near-normal GRN expression in haploinsufficient cells from human subjects …