For those who’d like to brush up on their knowledge of protein aggregation diseases, Chris Dobson of the University of Cambridge offers a quick tutorial in tomorrow’s Science. Dobson first raises the specter of acquired Creutzfeldt-Jakob disease in North America following reported cases of BSE in the US and Canada. He then goes on to lay out the approaches that are being developed to interfere with protein aggregation at various steps along the way.
These include small molecules or antibodies that either stabilize the native, soluble state of an otherwise aggregation-prone disease protein, or that speed the clearance of such proteins. The latter will be particularly important for natively unfolded proteins such as α-synuclein, which are deposited intact, without a distinct conformational conversion. Interventions based on preventing further fibril growth must ensure they do not inadvertently allow the accumulation of smaller, perhaps more toxic, oligomeric forms of the disease protein, Dobson writes. Finally, therapies could be developed that lengthen the time our natural defenses can stave off protein deposition. “This strategy perhaps could be considered a fist tentative step toward realizing the dream of the medieval alchemists to produce an elixir of life,” Dobson concludes optimistically.—Gabrielle Strobel
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