A new understanding of the way protein inhibitors work may have major implications in the development of drugs for Alzheimer's and other neurodegenerative diseases. Scientists have discovered a significant feature in the way that known amyloid inhibitors work, according to a paper to be published online this week in Nature Chemical Biology.
Several neurodegenerative diseases may be caused by the collection of various proteins into large clumps of disordered proteins, known as fibrils. A common strategy to try to find cures for these diseases is to search for molecules that can prevent formation of these fibrils or even cause them to break apart.
Brian Shoichet and colleagues demonstrate that the molecules that have been identified so far in this search act in an unusual manner: the compounds themselves form large groups, known as aggregates, which then act on the proteins to prevent the undesired clumping. The authors also found that other compounds not previously identified as amyloid inhibitors but known to form aggregates also stop the proteins from clumping up. This result will require a significant re-evaluation of the way in which drug developers approach Alzheimer's disease.
Brian Shoichet (University of California San Francisco, San Francisco, CA. USA)
Abstract available online.
(C) Nature Chemical Biology press release.
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