Ding, Lingzhi;Zhou, Jiamin;Ye, Lisa;Sun, Yechao;Jiang, Zhenglin;Gan, Deqiang;Xu, Lihua;Luo, Qianqian;Wang, Guohua published 《PPAR-γ Is Critical for HDAC3-Mediated Control of Oligodendrocyte Progenitor Cell Proliferation and Differentiation after Focal Demyelination》. The research results were published in《Molecular Neurobiology》 in 2020.Formula: C7H7NO3 The article conveys some information:
Disruption of remyelination contributes to neurodegeneration and cognitive impairment in chronically disabled patients. Valproic acid (VPA) inhibits histone deacetylase (HDAC) function and probably promotes oligodendrocyte progenitor cell (OPC) proliferation and differentiation; however, the relevant mol. mechanisms remain unknown. Here, focal demyelinating lesions (FDLs) were generated in mice by two-point stereotactic injection of lysophosphatidylcholine (LPC) into the corpus callosum. Cognitive functions, sensorimotor abilities and histopathol. changes were assessed for up to 28 days post-injury with or without VPA treatment. Primary OPCs were harvested and used to study the effect of VPA on OPC differentiation under inflammatory conditions. VPA dose-dependently attenuated learning and memory deficits and robustly protected white matter after FDL induction, as demonstrated by reductions in SMI-32 and increases in myelin basic protein staining. VPA also promoted OPC proliferation and differentiation and increased subsequent remyelination efficiency by day 28 post-FDL induction. VPA treatment did not affect HDAC1, HDAC2 or HDAC8 expression but reduced HDAC3 protein levels. In vitro, VPA improved the survival of mouse OPCs and promoted their differentiation into oligodendrocytes following lipopolysaccharide (LPS) stimulation. LPS caused OPCs to overexpress HDAC3, which translocated from the cytoplasm into the nucleus, where it directly interacted with the nuclear transcription factor PPAR-γ and neg. regulated PPAR-γ expression. VPA decreased the expression of HDAC3 and promoted remyelination and functional neurol. recovery after FDL. These findings may support the use of strategies modulating HDAC3-mediated regulation of protein acetylation for the treatment of demyelination-related cognitive dysfunction. The experimental procedure involved many compounds, such as N,2-Dihydroxybenzamide (cas: 89-73-6) .
N,2-Dihydroxybenzamide(cas: 89-73-6) is widely used for a variety of roles in biology and medicine as a chelating therapy.Formula: C7H7NO3It inhibits bacterial or fungi growth by interfering with iron uptake. It is also active as a inhibitor of enzyme involved in tumour growths.
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