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One step further toward treatment for degenerative diseases

18.05.2004


Scientists identify a key mechanism to recognize misfolded proteins



Scientists at McGill University’s Faculty of Medicine have discovered a key step that will provide new targets for treatments of many degenerative diseases such as Alzheimer’s, Cystic Fibrosis and Diabetes. Dr. David Thomas, Chair of Biochemistry, Dr. John Bergeron, Chair of Anatomy and Cell Biology and colleagues have identified a mechanism by which misfolded proteins are recognized in the cell. This is a critical process as proteins that are not correctly folded or shaped are extremely harmful to cells and are the basis for a number of human degenerative diseases. The findings were published in the prestigious journal Nature Structural and Molecular Biology.

"We have identified a central enzyme that is sensitive to very subtle changes in the folded state of a protein," explained Dr. David Thomas. "Proteins are the building blocks and machines of our bodies. In order for them to work correctly they have to fit together. Cells in our bodies have developed quality control mechanisms to assure proper folding. When something goes wrong, cells can accumulate misfolded proteins that don’t work properly. The misfolding of proteins is the basis for a number of neurodegenerative diseases such as Alzheimer’s and Parkinson’s. Our findings are an important step toward the development of innovative prevention and treatment strategies for such diseases."


Dr. Thomas and Dr. Bergeron, together with graduate student Sean Taylor and post-doctoral fellow Andrew Ferguson, showed that the enzyme UDP-glucose:glycoprotein glucosyltransferase (UGGT) can sense specific regions of disorder and activity of proteins – key steps to recognizing misfolded proteins and removing them from the cells.

The paper and accompanying News and Views are currently available online.


This study was supported by research grants from the Canadian Institutes of Health Research.

Dr. David Thomas (http://www.mcgill.ca/biochemistry/department/faculty/thomas/) is the Chair of the McGill Department of Biochemistry and holds a Canada Research Chair in Molecular Genetics. Dr. Thomas’ research focuses on cell signaling pathways and their role in infectious diseases, and on molecular chaperone systems in the endoplasmic reticulum.

McGill University (www.mcgill.ca) is Canada’s leading research-intensive university and has earned an international reputation for scholarly achievement and scientific discovery. The 21 faculties and professional schools offer more than 300 programs, from the undergraduate to the doctoral level, and our professors have received their education from leading academic centres around the world. There are approximately 23,000 full- and part- time undergraduate students and 7,000 full- and part-time graduate students. McGill was recently named Canadian Research University of the Year in the Medical/Doctoral category based on research funding and publication information compiled by Research Infosource.

The CIHR (www.cihr-irsc.gc.ca) is Canada’s premier agency for health research. Its objective is to excel, according to internationally accepted standards of scientific excellence, in the creation of new knowledge and its translation into improved health for Canadians, more effective health services and products and a strengthened health care system. CIHR’s Institute of Neurosciences, Mental Health and Addiction supports research to enhance mental health, neurological health, vision, hearing, and cognitive functioning and to reduce the burden of related disorders through prevention strategies, screening, diagnosis, treatment, support systems, and palliation.

Sandra McPherson | McGill University
Further information:
http://www.mcgill.ca/biochemistry/department/faculty/thomas/
http://www.mcgill.ca
http://www.cihr-irsc.gc.ca

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