[ Back to EurekAlert! ]

PUBLIC RELEASE DATE:
16-Apr-2009

[ | E-mail ] Share Share

Contact: Nick Zagorski
nzagorski@asbmb.org
301-634-7366
American Society for Biochemistry and Molecular Biology
@asbmb

Huntington disease begins to take hold early on

Appearing in the April 2009 issue of MCP

A global analysis of brain proteins over a 10-week period in a mouse model of Huntington Disease has revealed some new insights into this complex neurodegenerative disorder. For example, profound changes (comparable to those seen in late-stage HD) actually occur well before any disease symptoms show up, and most of the changes are confined to a specific stage during disease progression. These findings should aid in determining the optimal times for therapies that aim to treat or cure this disease.

While HD (which is brought on by mutations in the gene for Huntingtin has been studied extensively at the cellular level, much of the work has been focused on late-stage disease when the various symptoms (declines in both motor coordination and cognitive ability) have already manifested. But since HD is an inherited condition, changes likely occur much earlier, and to get a better sense of disease progression, Claus Zabel and colleagues used proteomics to analyze the brains of HD mice at 2, 4, 6, 8, and 12 weeks of age, a period that covers absence of any disease-related phenotypes to the pronounced disease state.

Unexpectedly, they found a large number of protein alterations (almost 6% of the total) as early as 2 weeks of age; a significant portion of these changes contributed to an increase in glucose metabolism, which corresponds to the weight loss that occurs early during HD progression. As the disease progressed over 10 weeks, though, the affected proteins kept changing. In fact, about 70% of observed changes were confined to one of the five time points examined and no proteins were similarly altered in all 5 stages.

Therefore this study, appearing in the April issue of Molecular and Cellular Proteomics, argues against an HD model in which there is a gradual increase in the number and magnitude of protein changes and instead leans toward a more dynamic pathology. Zabel and colleagues suggest that these early changes affect late stage disease by irreversibly changing the biochemical activity in the mouse brain.

###

From the study: "A Large Number of Protein Expression Changes Occur Early in Life and Precede Phenotype Onset in a Mouse Model for Huntington Disease" by Claus Zabel, Lei Mao, Ben Woodman|, Michael Rohe, Maik A. Wacker, Yvonne Kläre, Andrea Koppelstätter, Grit Nebrich, Oliver Klein, Susanne Grams, Andrew Strand, Ruth Luthi-Carter, Daniela Hartl, Joachim Klose and Gillian P. Bates

Corresponding Author: Claus Zabel, Institute for Human Genetics, Charité-Universiy Medicine Berlin, Germany. Tel.: 49-30-450-566258; E-mail: claus.zabel@charite.de

Article Link: http://www.mcponline.org/cgi/content/full/8/4/720

The American Society for Biochemistry and Molecular Biology is a nonprofit scientific and educational organization with over 11,900 members in the United States and internationally. Most members teach and conduct research at colleges and universities. Others conduct research in various government laboratories, nonprofit research institutions and industry. The Society's student members attend undergraduate or graduate institutions.

Founded in 1906, the Society is based in Bethesda, Maryland, on the campus of the Federation of American Societies for Experimental Biology. The Society's purpose is to advance the science of biochemistry and molecular biology through publication of the Journal of Biological Chemistry, the Journal of Lipid Research, and Molecular and Cellular Proteomics, organization of scientific meetings, advocacy for funding of basic research and education, support of science education at all levels, and promoting the diversity of individuals entering the scientific work force.

For more information about ASBMB, see the Society's Web site at www.asbmb.org.



[ Back to EurekAlert! ] [ | E-mail Share Share ]

 


AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert! system.