Aptamer Reduces Aggregation of Mutant Huntingtin and Rescues Proteostasis Network in Non-Neuronal and Neuronal Cells
Swati Jain, Ipsita Roy
Abstract
Aggregation of mutant huntingtin is a pathological hallmark of Huntington's disease (HD). Protein aggregation results in various cellular dysfunctions, such as increase in oxidative stress, mitochondrial damage, proteostasis imbalance, etc., which finally cause cell death. Previously, specific RNA aptamers with high affinity for mutant huntingtin were selected. In the current study, we show that the selected aptamer inhibits aggregation of mutant huntingtin (EGFP-74Q) in HEK293 and Neuro 2a cell models of HD. The presence of aptamer decreases sequestration of chaperones and increases their cellular levels. This is accompanied by improved mitochondrial membrane permeability, reduced oxidative stress, and increased cell survival. Thus, RNA aptamers can be explored further as inhibitors of protein aggregation in protein misfolding diseases.