Investigating Whether the Improvement of the AMP-Activated Protein Kinase (AmpK) is Neuroprotective in Huntington’s Disease Neurons

Abstract

Huntington’s disease (HD) is a hereditary condition which causes disordered movement, behavioral changes, and dementia. As with many neurological diseases, there is no effective treatment and HD is universally fatal. Metformin has been found improve cognitive score in diabetic patients with HD and has also improved motor function and decreased mutant HTT aggregates in mice brains. Like metformin, BC1618 is an inhibitor of Fbxo48 and its potency in stimulating Ampk-dependent signaling greatly exceeds metformin. GA100 also works in a similar manner as BC1618. Thus, Q7 and Q111 cell lines were treated with 5 and 10 μM concentrations of BC1618 or GA1000 and the samples were collected to perform protein, RNA, and DNA analysis. The most significant results from this experiment came from the qPCR results which confirmed the initial hypothesis and supported the idea that both BC1618 and GA100 effectively inhibit Fbxo48 and prolong Ampk activation. We further hypothesize that this will promote mitochondrial biogenesis which can have neuroprotective effects on HD.