Misfolding the way to disease
Taubes, G.
Science 271(5255): 1493-1495
1996
ISSN/ISBN: 0036-8075 PMID: 8599100 Document Number: 456135
The relationship between protein misfolding and amyloid diseases is discussed. Over the past few years, studies of how proteins fold have led to the realization that the way protein clumps form in test tubes is astonishingly similar to the way proteins form the so-called amyloid deposits that are the pathological hallmarks of some dozen different diseases, the best known of which is Alzheimer's. The new studies suggest that test tube protein aggregation and amyloid diseases result when something goes wrong with normal protein folding, allowing incompletely folded protein molecules to latch onto each other and to self-assemble into insoluble fibril aggregates. The buildup of those aggregates in living tissue, which can be promoted by mutations that either alter how the protein folds initially or destabilize its final structure, can ultimately prove fatal. Potential treatments that work by preventing protein misfolding are discussed.