期刊
JOURNAL OF NEUROIMMUNOLOGY
卷 164, 期 1-2, 页码 10-21出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jneuroim.2005.02.022
关键词
multiple sclerosis; histone deacetylase; trichostatin A; microarrays; experimental autoimmune encephalomyelitis
资金
- NCI NIH HHS [1K08-CA80084] Funding Source: Medline
- NINDS NIH HHS [NS045242, NS045806, R21-NS41623] Funding Source: Medline
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. (C) 2005 Elsevier B.V. All rights reserved.
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