Protein Expression in the Striatum and Cortex Regions of the Brain for a Mouse Model of Huntington's Disease

Liquid chromatography (LC) coupled with mass spectrometry (MS) and database assignment methods
have been used to conduct a large-scale proteome survey of the R6/2 mouse model of Huntington's
disease (HD). Although the neuropathological mechanisms of HD are not known, the mutant huntingtin
gene that causes the disease is thought to alter gene transcription, leading to a cascade of neurotoxic
events. In this report, we have focused on characterizing changes in the brain proteome associated
with HD pathophysiology. Differences in the relative abundances of proteins (R6/2 compared to wild
type) in brain tissue from the striatum and cortex, two primary loci of dysfunction in HD, were assessed
by using a label-free approach based on calibrations to internal standards. In total, assignments were
made for ∼400 proteins. A set of criteria was used to establish 160 high confidence assignments, ∼30%
of which appear to show differences in expression relative to wild type (WT) animals. Many of the
proteins that were differentially expressed are known to be associated with neurotransmission and
likely play key roles in HD etiology. This study is the first to report that the majority of differentially
expressed proteins in the striatum are up-regulated, while the majority of the expressed proteins in
the cortex are down-regulated. The differentially expressed proteins identified in this proteomic screen
may be potential biomarkers and drug targets for HD and may further our understanding of the disease
pathology.
Keywords: Huntington's disease · liquid chromatography · mass spectrometry · brain proteome · label-free
quantification · striatum · cortex