Quantitative Proteomic Analysis Reveals Similarities between Huntington's Disease (HD) and Huntington's Disease-Like 2 (HDL2) Human Brains

Tamara Ratovitski, Raghothama Chaerkady, Kai Kammers, Jacqueline C. Stewart, Anialak Zavala, Olga Pletnikova, Juan C. Troncoso, Dobrila Rudnicki, Russell L. Margolis, Robert N. Cole, Christopher A. Ross

Research output: Contribution to journalArticle

Abstract

The pathogenesis of HD and HDL2, similar progressive neurodegenerative disorders caused by expansion mutations, remains incompletely understood. No systematic quantitative proteomics studies, assessing global changes in HD or HDL2 human brain, were reported. To address this deficit, we used a stable isotope labeling-based approach to quantify the changes in protein abundances in the cortex of 12 HD and 12 control cases and, separately, of 6 HDL2 and 6 control cases. The quality of the tissues was assessed to minimize variability due to post mortem autolysis. We applied a robust median sweep algorithm to quantify protein abundance and performed statistical inference using moderated test statistics. 1211 proteins showed statistically significant fold changes between HD and control tissues; the differences in selected proteins were verified by Western blotting. Differentially abundant proteins were enriched in cellular pathways previously implicated in HD, including Rho-mediated, actin cytoskeleton and integrin signaling, mitochondrial dysfunction, endocytosis, axonal guidance, DNA/RNA processing, and protein transport. The abundance of 717 proteins significantly differed between control and HDL2 brain. Comparative analysis of the disease-associated changes in the HD and HDL2 proteomes revealed that similar pathways were altered, suggesting the commonality of pathogenesis between the two disorders.

Original languageEnglish (US)
Pages (from-to)3266-3283
Number of pages18
JournalJournal of Proteome Research
Volume15
Issue number9
DOIs
StatePublished - Sep 2 2016

Keywords

  • human brain
  • Huntington's disease
  • iTRAQ
  • neurodegenerative disorder
  • proteomics
  • TMT

ASJC Scopus subject areas

  • Biochemistry
  • Chemistry(all)

Fingerprint Dive into the research topics of 'Quantitative Proteomic Analysis Reveals Similarities between Huntington's Disease (HD) and Huntington's Disease-Like 2 (HDL2) Human Brains'. Together they form a unique fingerprint.

  • Cite this