Suberoylanilide Hydroxamic Acid (Vorinostat) Up-regulates Progranulin Transcription
2011; Elsevier BV; Volume: 286; Issue: 18 Linguagem: Inglês
10.1074/jbc.m110.193433
ISSN1083-351X
AutoresBasar Cenik, Chantelle F. Sephton, Colleen M. Dewey, Xunde Xian, Shuguang Wei, Kimberley Yu, Wenze Niu, Giovanni Coppola, Sarah Coughlin, Suzee E. Lee, Daniel R. Dries, Sandra Almeida, Daniel H. Geschwind, Fen‐Biao Gao, Bruce L. Miller, Robert V. Farese, Bruce A. Posner, Gang Yu, Joachim Herz,
Tópico(s)Sulfur-Based Synthesis Techniques
ResumoProgranulin (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. Although elevation of secreted progranulin levels through a post-transcriptional mechanism has recently been reported, this is, to the best of our knowledge, the first report of a small molecule enhancer of progranulin transcription. SAHA has demonstrated therapeutic potential in other neurodegenerative diseases and thus holds promise as a first generation drug for the prevention and treatment of frontotemporal dementia.
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