MicroRNA-27a reduces mutant hutingtin aggregation in an in vitro model of Huntington's disease
Abstract
Huntington's disease (HD) is a fatal genetic disease caused by abnormal aggregation of mutant huntingtin protein (mHtt). Reduction of mHtt aggregation decreases cell death of the brain and is a promising therapeutic strategy of HD. MicroRNAs are short non-coding nucleotides which modulate various genes and dysregulated in many diseases including HD. MicroRNA miR-27a was reported to be reduced in the brain of R6/2 HD mouse model and modulate multidrug resistance protein-1 (MDR-1). Using subventricular zone-derived neuronal stem cells (NSCs), we used in vitro HD model to test the effect of miR-27a on MDR-1 and mHtt aggregation. R6/2-derived NSCs can be differentiated under condition of growth factor deprivation, and the progression of differentiation leads to a decrease of MDR-1 level and efflux function of cells. Immunocytochemistry result also confirmed that mHtt aggregation was increased with differentiation. We transfected miR-27a in the R6/2-derived differentiated NSCs, and examined phenotype of HD, mHtt aggregation. As a result, miR-27a transfection resulted in reduction of mHtt aggregation in HD cells. In addition, MDR-1, which can transport mHtt, protein level was increased by miR-27a transfection. Conversely, knock-down ...Continue Reading
References
Down-regulation of miR-27a might reverse multidrug resistance of esophageal squamous cell carcinoma.
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