Ever since Alois Alzheimer and his colleagues first described abnormal aggregates of the amyloid protein in the brain of a patient who died of a form of dementia now known as Alzheimer's disease, biochemists have been fascinated by the molecular events associated with such protein misfolding. They hope that understanding the molecular basis of protein misfolding will aid the development of drugs against not only Alzheimer's disease, but also a range of disorders caused by mis-folded proteins. These are known collectively as conformational diseases and include prion diseases, Parkinson's disease, Huntington's disease and several disorders known as ser-pinopathies1. Whereas Alzheimer's disease and certain related disorders are caused by misfolded amyloid, serpinopathies - which include the respiratory disease emphysema, early-onset dementia and liver cirrhosis - are caused by polymerization of serpin proteins. On page 1255 of this issue, Yamasaki et al. show how serpins misfold into serpinopathy-causing polymers.
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