LAMP2A-mediated autophagy involved in Huntington's disease progression

Huntington's disease (HD) is caused by a mutant huntingtin (mHtt) protein that contains abnormally extended polyglutamine (polyQ) repeats. The process of autophagy has been implicated in clearing mHtt aggregates, and microRNAs (miRNAs) have been reported as new players to regulate autophagy. However, the autophagy-associated target molecule of let7b miRNA remains unclear in HD. The present study showed that extended polyQ in mouse striatal neurons increased lysosomal membrane-associated protein 2A (LAMP2A) levels and influenced the inflammatory conditions, and these augmented levels correlated to the let7b miRNA expression level. The upregulated let7b increased LAMP2A and reduced the extended polyQ in mouse striatal cells. The let7b level was highly expressed in the striatum of preonset HD mice, whereas it was significantly reduced in the post-onset HD striatum. Considering the level changing pattern of let7b, LAMP2A protein levels were increased in the striatum of pre-onset HD mice, but decreased in the striatum of post-onset HD mice. These results suggest that LAMP2A related to chaperone-mediated autophagy (CMA) capacity might play an important role in HD symptom onset and progression. (C) 2020 Elsevier Inc. All rights reserved.

Automated summary

The study demonstrated that let7b miRNA can increase LAMP2A and reduce extended polyQ in mouse striatal cells. The level of let7b was highly expressed in the striatum of pre-onset HD mice, but significantly reduced in post-onset HD mice. These findings suggest that LAMP2A related to chaperone-mediated autophagy (CMA) capacity may play a crucial role in the onset and progression of HD symptoms.