Mouse model confirms mutated protein's role in dementia

November 02, 2010

A team of scientists from Japan and the University of California, San Diego School of Medicine have created a new mouse model that confirms that mutations of a protein called beta-synuclein promote neurodegeneration. The discovery creates a potential new target for developing treatments of diseases like Parkinson's and Alzheimer's.

The work is published in today's issue of Nature Communications. Lead author is Makoto Hashimoto of the Division of Chemistry and Metabolism, Tokyo Metropolitan Institute for Neuroscience, with colleagues including Eliezer Masliah, MD, professor of neurosciences and pathology in the UC San Diego School of Medicine, Edward Rockenstein, a research associate in UCSD's Experimental Neuropath Laboratory and Albert R. La Spada, MD, PhD, professor of cellular and molecular medicine, chief of the Division of Genetics in the Department of Pediatrics and associate director of the Institute for Genomic Medicine at UC San Diego.

In 2004, La Spada discovered mutations in a family afflicted with a neurological disorder known as Dementia with Lewy Bodies. DLB is one of the most common types of progressive dementia, combining features of both Alzheimer's and Parkinson's diseases. Lewy bodies are abnormal aggregates of proteins. There are no known therapies to stop or slow the DLB's progression. There is no cure.

In the 2004 study, La Spada and colleagues found that mutations of the naturally occurring B-synuclein protein in DLB patients "were strong strongly suggestive of being pathogenic." That is, the mutated protein caused or was a cause of the disease. But the findings were not definitive.

The newly published research describes the creation of a transgenic mouse model that expresses the B-synuclein mutation. The mice suffer from neurodegenerative disease, validating La Spada's earlier work.

"Beta-synuclein is interesting because it is closely related to alpha-synuclein, a protein that can cause Parkinson's disease by being mutated or over-expressed," said La Spada. "A-synuclein is viewed as central to Parkinson's disease pathogenesis. The question has been: could B-synuclein also promote neurodegeneration because it's similar in its sequence and expression pattern to A-synuclein? This study shows that the answer is yes."

These findings, said La Spada, establish B-synuclein's links to Parkinson's disease and related disorders, making it a new and, now, proven target for potential therapies.
-end-
Co-authors of the study are Masaya Fujita, Shuei Sugama, Kazunari Sekiyama, Akio Sekigawa, Masaaki Nakai, Masaaki Waragai, Yoshiki Takamatsu and Jianshe Wei of the Division of Chemistry and Metabolism, Tokyo Metropolitan Institute for Neuroscience; Tohru Tsukui of the Division of Gene Regulation and Signal Transduction, Research Center for Genomic Medicine, Saitama Medical University; Takato Takenouchi of the Division of Chemistry and Metabolism, Tokyo Metropolitan Institute for Neuroscience and the Transgenic Animal Research Center, National Institute of Agrobiological Sciences in Japan; and Satoshi Inoue of Division of Gene Regulation and Signal Transduction, Research Center for Genomic Medicine, Saitama Medical University and Department of Anti-Aging, Graduate School of Medicine, University of Tokyo.

Funding for this study came in part from grants by Science Research, the Cell Innovation Project; Challenging Exploratory Research, the National Institute of Biomedical Innovation, the Takeda Foundation, the Novartis Foundation for Gerontological Research and the National Institutes of Health.

University of California - San Diego

Related Dementia Articles from Brightsurf:

The danger of Z-drugs for dementia patients
Strong sleeping pills known as 'Z-drugs' are linked with an increased risk of falls, fractures and stroke among people with dementia, according to new research.

The long road to dementia
Alzheimer's disease develops over decades. It begins with a fatal chain reaction in which masses of misfolded beta-amyloid proteins are produced that in the end literally flood the brain.

Why people with dementia go missing
People with dementia are more likely to go missing in areas where road networks are dense, complicated and disordered - according to new research from the University of East Anglia.

PTSD may double risk of dementia
People who have experienced post-traumatic stress disorder (PTSD) are up to twice as likely to develop dementia later in life, according to a new study by UCL researchers, published in the British Journal of Psychiatry.

Dementia education
School-based dementia education could deliver much needed empathy and understanding for older generations as new research from the University of South Australia shows it can significantly improve dementia knowledge and awareness among younger generations.

Building dementia friendly churches
A project to help church communities become more 'dementia friendly' has had a significant impact across the country.

A "feeling" for dementia?
A research team led by the DZNE concludes that personal perception can be an important indicator for the early detection of Alzheimer's disease.

New biomarker for dementia diagnosis
Medical researchers in the UK and Australia have identified a new marker which could support the search for novel preventative and therapeutic treatments for dementia.

Digital solutions for dementia care
Telehealth delivery of dementia care in the home can be as effective as face-to-face home visit services if carers and recipients take advantage of the technologies available, Australian researchers say.

Despite a marked reduction in the prevalence of dementia, the number of people with dementia is set to double by 2050 according to new Alzheimer Europe report
Today, at a European Parliament lunch debate, Alzheimer Europe launched a new report presenting the findings of its collaborative analysis of recent prevalence studies and setting out updated prevalence rates for dementia in Europe.

Read More: Dementia News and Dementia Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.