Huntington disease begins to take hold early on

April 16, 2009

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 , 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.

More information: www.mcponline.org/cgi/content/full/8/4/720

Source: American Society for Biochemistry and Molecular Biology

Related Stories

Recommended for you

Study seeks to aid diagnosis, management of catatonia

December 11, 2017
Catatonia, a syndrome of motor, emotional and behavioral abnormalities frequently characterized by muscular rigidity and a trance-like mental stupor and at times manifesting with great excitement or agitation, can occur during ...

New compound stops progressive kidney disease in its tracks

December 7, 2017
Progressive kidney diseases, whether caused by obesity, hypertension, diabetes, or rare genetic mutations, often have the same outcome: The cells responsible for filtering the blood are destroyed. Reporting today in Science, ...

New Lyme disease tests could offer quicker, more accurate detection

December 7, 2017
New tests to detect early Lyme disease - which is increasing beyond the summer months -could replace existing tests that often do not clearly identify the infection before health problems occur.

Spinal tap needle type impacts the risk of complications

December 6, 2017
The type of needle used during a lumbar puncture makes a significant difference in the subsequent occurrence of headache, nerve irritation and hearing disturbance in patients, according to a study by Hamilton medical researchers.

Men with HPV are 20 times more likely to be reinfected after one year

December 5, 2017
A new analysis of genital human papillomavirus (HPV) in men shows that infection with one HPV type strongly increases the risk of reinfection with the same type. In fact, men who are infected with the type responsible for ...

New tuberculosis drugs possible with understanding of old antibiotic

December 5, 2017
Tuberculosis, and other life-threatening microbial diseases, could be more effectively tackled with future drugs, thanks to new research into an old antibiotic by the University of Warwick and The Francis Crick Institute.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.