Novel aggregation-specific fluorogen monitors prefibrillar protein aggregation by fluorescence polarisation (FP)

Highly ordered protein aggregates, termed amyloid fibrils, are associated with a broad range of diseases, many of which are neurodegenerative, for example, Alzheimer’s and Parkinson’s. The transition from soluble, functional protein to insoluble amyloid fibril occurs via a complex process involving the initial generation of highly dynamic early stage aggregates or prefibrillar species. Prefibrillar species (dimers, tetramers etc.) are proposed to play a key role in the cytotoxicity of amyloid fibrils. Therefore, novel probes that have broad applicability in the detection of prefibrillar species of amyloidogenic proteins are actively being sought.

Recently, a novel broad-spectrum fluorescent probe was presented: (bis(triphenylphosphonium) tetraphenylethene (TPE-TPP)), with emission characteristics that are eminently suited to monitoring prefibrillar aggregation of various protein species using various fluorescence techniques. It is shown that TPE-TPP-based FP measurements can monitor the fibrillar assembly of a variety of amyloid fibril-forming proteins in situ.