The amyloid precursor protein and its homologues: Structural and functional aspects of native and pathogenic oligomerization

摘要: Over the last 25 years, remarkable progress has been made not only in identifying key molecules of Alzheimer's disease but also understanding their meaning pathogenic state. One hallmark Alzheimer pathology is amyloid plaque. A major component extracellular deposit amyloid-β (Aβ) peptide which generated from its larger precursor molecule, i.e., protein (APP) by consecutive cleavages. Processing exerted two enzymes, β-secretase and γ-secretase. We others have found that self-association dimerization oligomerization these proteins a factor under native conditions. In particular, Aβ homodimer represents nidus for plaque formation well defined therapeutic target. Further, APP was reported to increase generation toxic whereas heterodimerization with homologues like (APLP1 APLP2) decreased formation. This review mainly focuses on structural features homophilic heterophilic interactions among family proteins. The proposed contact sites are described consequences functions pathogenesis discussed.