We demonstrate that the histone deacetylase (HDAC) inhibitor drug trichostatin A (TSA) reduces spinal cord inflammation, demyelination, neuronal and axonal loss and ameliorates disability in the relapsing phase of experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis (MS). TSA up-regulates antioxidant, anti-excitotoxicity and pro-neuronal growth and differentiation mRNAs. TSA also inhibits caspase activation and down-regulates gene targets of the pro-apoptotic E2F transcription factor pathway. In splenocytes, TSA reduces chemotactic, pro-Th1 and pro-proliferative mRNAs. A transcriptional imbalance in MS may contribute to immune dysregulation and neurodegeneration, and we identify HDAC inhibition as a transcriptional intervention to ameliorate this imbalance.
Transcriptional therapy with the histone deacetylase inhibitor trichostatin A ameliorates experimental autoimmune encephalomyelitis
Autor(es):
Sandra Camelo 1, Antonio H Iglesias, Daehee Hwang, Brice Due, Hoon Ryu, Karen Smith, Steven G Gray, Jaime Imitola, German Duran, Basel Assaf, Brett Langley, Samia J Khoury, George Stephanopoulos, Umberto De Girolami, Rajiv R Ratan, Robert J Ferrante, Fernando Dangond
Patologia:
Doenças Autoimunes
Link do Artigo:
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Data de Criação:
17/05/2022
Data de Publicação:
27/03/2025