Amyloid oligomers: spectroscopic characterization of amyloidogenic protein states

摘要: It is assumed that protein fibrils manifested in amyloidosis result from an aggregation reaction involving small misfolded sequences being 'oligomeric' or 'prefibrillar' state. This review covers recent optical spectroscopic studies of amyloid misfolding, oligomerization and fibril growth. Although have been studied using established protein-characterization techniques throughout the years, their oligomeric precursor states require sensitive detection real-time. Here, fluorescent staining commonly performed thioflavin T other molecules such as 4-(dicyanovinyl)- julolidine 1-amino-8-naphtalene sulphonate high affinity to hydrophobic patches. Thus, populated intermediates related 'prefibrillar structures' reported for several human amyloidogenic systems, including amyloid-beta protein, prion transthyretin, alpha-synuclein, apolipoprotein C-II insulin. To obtain information on progression intermediate states, these were monitored terms fluorescence parameters, anisotropy, quantum efficiency changes upon binding. Recently, new antibody stains allowed precise monitoring oligomer size distributions multicolor labelling single molecule detection. Moreover, a pentameric thiophene derivative (p-FTAA) was indicate early precursors during A-beta(1-40) fibrillation, also demonstrated real-time visualization cerebral aggregates transgenic AD mouse models by multiphoton microscopy. Conclusively, molecular probes spectroscopy are now entering phase enabling vivo interrogation role oligomers amyloidosis. Such used parallel with vitro experiments, increasing detail, will probably couple structure pathogenesis near future.