A large number of protein expression changes occur early in life and precede phenotype onset in different animal models for Huntington's disease

Abstract

Huntington's disease (HD) is fatal in humans within 15 to 20 years of symptomatic disease. Although late stage HD has been studied extensively, protein expression changes that occur at the early stages of disease and during disease progression have not been reported. In this study, we used a large 2‐D gel/mass spectrometry based proteomics approach to investigate HD‐induced protein expression alterations and their kinetics at very early stages and during the course of disease. Different HD animal models were investigated at absence, early, intermediate and late stage HD. Preliminary results showed that in at least two animal models HD‐stage‐specific protein changes (above 70%) as well as a drastic alteration in protein expression already occurred before symptoms appeared. Early changes included in both cases the dys‐regulation of proteins involved in glycolysis/gluconeogenesis and the actin‐cytoskeleton formation. This suggests a period of highly variable protein expression which precedes the onset of an HD phenotype. More animal models will be investigated to further characterize protein alteration kinetics and their role in HD. Our observations suggest that HD is characterized by a highly dynamic disease pathology not represented by linear protein concentration alterations over the course of disease.