New publication - PREP inhibition reduces huntingtin aggregation in a Huntington's disease model!

Our study "Prolyl oligopeptidase inhibition reduces PolyQ aggregation and improves cell viability in cellular model of Huntington's disease" that was performed in collaboration with Prof. Dan Lindholm (University of Helsinki) was published in Journal of Cellular and Molecular Medicine. In this publication, we show that PREP inhibition reduces the aggregation and toxicity of mutant huntingtin in a cellular model.

Huntington's disease is a genetic neurodegenerative disease where a gene coding huntingtin-protein is mutated and starts to generate long "tail" to the protein. This leads to huntingtin aggregation, neuronal death and severe symptoms, and current drug therapies cannot slow the progress of the diseases that leads to death in 5-10 years after diagnosis. We have earlier shown that PREP inhibition can reduce alpha-synuclein aggregates by enhancing the functionality of cellular "recycling center", autophagy. Since protein aggregation is aski having a major role in Huntington's disease, we wanted to test if PREP inhibition could reduce mutant-huntingtin aggregation.

When cells expressing mutant-huntingtin were exposed to PREP inhibition, the levels of protein aggregates were lowered and cells also had better viability. This was probably due the enhanced cellular recycling and degradation of huntingtin aggregates. Taken together, this indicates that PREP inhibition may be applicable to several neurodegenerative diseases with protein aggeregates, not only on Parkinson's disease.

Publication is available for everybody as open access in journal website - click here to read it: