Therapeutic amyloid fibrils

DESCRIPTION (provided by applicant): Accumulation of amyloid fibrils correlates with neurodegeneration in various brain diseases, but the biological role of the fibrils is unclear. Our previous experiments established that amyloidogenic peptides from thesmall heat shock protein, HspB5, and from Amyloid ? fibrils, characteristic of Alzheimer's disease, were therapeutic when administered systemically in experimental autoimmune encephalomyelitis (EAE), which models aspects of neuroinflammation in multiple sclerosis. The minimal structural units for the therapeutic amyloid fibrils are peptides as short as hexamers, which are capable of forming cross beta sheet steric zippers, but not the complex super secondary structures, torroids, cylindrins, and ? barrels,inherent in protein based amyloids that result in cellular cytotoxicity. The minimal fibrils are molecular chaperones, inhibiting protein aggregation in plasma, which reduces the gene expression of a spectrum of proinflammatory mediators. In addition,