Progressive demyelination in multiple sclerosis (MS) reflects the negative balance between myelin damage and repair due to physical and molecular barriers, such as astrocytic glial scars, between oligodendrocytes and target neurons. In this paper, we show that combination therapy with paclitaxel (Taxol®) plus the universal methyl-donor, vitamin B12CN (B12CN), dramatically limits progressive demyelination, and enhances remyelination in several independent, immune and nonimmune, in vivo and in vitro model systems. Combination therapy significantly reduced clinical signs of EAE in SJL mice, as well as the spontaneously demyelinating ND4 transgenic mouse. Astrocytosis was normalised in parallel to ultrastructural and biochemical evidence of remyelination. The combination therapy suppressed T cell expansion, reduced IFN-gamma, while enhancing IFN-beta and STAT-1 expression, STAT-1 phosphorylation and methylation of STAT-1 and MBP in the brain. Paclitaxel/B12CN has nearly identical effects to the previously des...

Synergy between paclitaxel plus an exogenous methyl donor in the suppression of murine demyelinating diseases.

Nucleosome is the basic unit of chromatin. Nucleosome repression on gene transcription is a dominant factor in the tissue or cell type specific expression on a gene from the whole genome of an eukaryote. Derepression of chromatin to an open conformation may lead to the promotion of gene transcription. The nature of chromatin remodeling, the role of histone acetyltransferase and deacetylase, the repression mechanisms of chromatin induced by the methylated CpG binding proteins are discussed in this paper. The role of chromatin in the pathogenesis of diseases has attracted broad interests from the clinicians. Cis-elements of chromatin DNA helps defining the functional segments within the genome, which provide indispensable evidences to bio-informatics, and to the linkage between genomics and proteomics. Additionally, in vitro assembly of chromatin from multiple bio-active molecules to display new functions on gene activity indicates the growing importance of integrating studies in life sciences in the coming century.

Chromatin structure and gene activation

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Chromatin structure and gene activation