Cellular Waste Disposal a Target for Drug Therapies
Proteins that are defectively produced and misfolded and no longer function properly must be disposed to prevent damage. This is true also for “healthy” functional proteins that must be removed when they are no longer needed – when the processes they control must be stopped.
Thus, the body simultaneously generates and disposes of numerous proteins. The disposal process is a highly controlled one and conducted by the ubiquitin-proteasome system. Proteins prone for disposal are labelled with the molecule ubiquitin and transported to the proteasomes where they are then chopped into pieces and destroyed.
Aberrations in this important cellular waste disposal can lead to a wide array of diseases ranging from cancer to neurodegenerative disorders such as some forms of Alzheimer’s and Parkinson’s Disease, genetic diseases such as cystic fibrosis, and different immune and inflammatory disorders. “Because of its crucial role for many basic cellular processes, it is very challenging to develop drugs which can modulate this system”, Professor Ciechanover said in his keynote lecture at the New Year’s Reception of the Berlin-Buch Campus at the Max Delbrück Communications Center (MDC.C) in Berlin, Germany on Friday, January 19, 2007.
The physician and biologist from the Faculty of Medicine of the Technion Israel Institute of Technology in Haifa, Israel is one the discoverers of the ubiquitin-proteasome system and shared the Nobel Prize in Chemistry in 2004 for this pioneering research. Professor Ciechanover pointed out that one successful drug to combat multiple myeloma, a form of leukaemia (blood cancer), is already on the market and has revolutionized the treatment of this disease. The drug, Velcade (Bortezomib) is a proteasome inhibitor.
It was licensed in the USA in 2003 and was also approved in Germany in 2004. The drug inhibits the degradation of certain abnormal proteins resulting in the literal suffocation of the tumor cells in their own protein waste. Professor Ciechanover is convinced that a better understanding of the very complex processes and the identification of the components involved in the degradation of key regulatory proteins will eventually lead to the development of novel, mechanism-based drugs that will target only the involved proteins. Aaron Ciechanover was born in Haifa, Israel on October 1, 1947. He received his Doctor`s degree in medicine in 1975 at the Hebrew University of Jerusalem, and his doctoral degree in biology in 1982 at the Technion Israel Institute of Technology in Haifa. He is Distinguished Professor at the Center for Cancer and Vascular Biology, the Rappaport Faculty of Medicine and Research Institute at the Technion.
Barbara Bachtler
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