Alzheimer's and prion disease as disorders of protein conformation: implications for the design of novel therapeutic approaches

Several lines of evidence suggest that a defective protein folding is a cen tral event in both Alzheimer's and prion disease. Although the two disorder s are very different clinically, neuropathologically, and biochemically, th e molecular event that may trigger the disease process appears to be the sa me: the formation of an altered protein conformer composed of a high conten t of P-sheet structure. Compounds with the ability to prevent and to revers e protein conformational changes may be useful as novel therapeutic approac hes for Alzheimer's disease, prion disease, and other disorders of defectiv e protein folding.