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STUDY: One Step Further Toward Treatment For Degenerative Diseases
Public release date: 17-May-2004
Contact: Sandra McPherson
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McGill University

One step further toward treatment for degenerative diseases

Scientists identify a key mechanism to recognize misfolded proteins

Montreal, May 17, 2004 - 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.

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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 http://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 http://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.

SOURCE: EurekAlert, DC
http://www.eurekalert.org/pub_releases/2004-05/mu-osf051704.php

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