MicroRNA-146a: a potential therapeutic target in multiple sclerosis

Snelgrove, Andrew Michael Graham (2018) MicroRNA-146a: a potential therapeutic target in multiple sclerosis. Masters thesis, Memorial University of Newfoundland.

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Abstract

Multiple sclerosis (MS) is a neuroinflammatory disease characterized by demyelinated neurons in the central nervous system. Decreased levels of the anti-inflammatory microRNA-146a have previously been observed in macrophages/microglia in MS patients compared to controls. Therapeutically elevating microRNA-146a expression in MS may produce a conducive environment for remyelination. Inflammatory cytokines were assessed from both primary mouse and human macrophages and microglia, and THP-1 macrophages that were transfected with a microRNA-146a mimic and polarized towards a pro-inflammatory phenotype. Inflammatory cytokines and MS-relevant targets were measured following activation; neuro- and oligodendrogenesis were also assessed in vitro while the effect of microRNA-146a on myelin phagocytosis was also examined. MicroRNA-146a may decrease pro-inflammatory TNF but may have little to no effect on IL-6; RhoA may decrease in both mouse and human macrophages. MicroRNA-146a increased myelin phagocytosis of unstimulated primary mouse microglia. Finally, in vitro experiments suggest that supernatants collected from LPS-stimulated murine macrophages transfected with a microRNA-146a mimic do not affect neurogenesis or oligodendrogenesis. It is suggested that increasing microRNA-146a may promote an anti-inflammatory environment beneficial for promoting remyelination in MS.

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