TY - JOUR T1 - Amyloid Fibrils Composed of Hexameric Peptides Attenuate Neuroinflammation JF - Science Translational Medicine SP - 179ra42 LP - 179ra42 DO - 10.1126/scitranslmed.3005681 VL - 5 IS - 179 AU - Kurnellas, Michael P. AU - Adams, Chris M. AU - Sobel, Raymond A. AU - Steinman, Lawrence AU - Rothbard, Jonathan B. Y1 - 2013/04/03 UR - http://stm.sciencemag.org/content/5/179/179ra42.abstract N2 - The amyloid-forming proteins tau, αB crystallin, and amyloid P protein are all found in lesions of multiple sclerosis (MS). Our previous work established that amyloidogenic peptides from the small heat shock protein αB crystallin (HspB5) and from amyloid β fibrils, characteristic of Alzheimer’s disease, were therapeutic in experimental autoimmune encephalomyelitis (EAE), reflecting aspects of the pathology of MS. To understand the molecular basis for the therapeutic effect, we showed a set of amyloidogenic peptides composed of six amino acids, including those from tau, amyloid β A4, major prion protein (PrP), HspB5, amylin, serum amyloid P, and insulin B chain, to be anti-inflammatory and capable of reducing serological levels of interleukin-6 and attenuating paralysis in EAE. The chaperone function of the fibrils correlates with the therapeutic outcome. Fibrils composed of tau 623–628 precipitated 49 plasma proteins, including apolipoprotein B-100, clusterin, transthyretin, and complement C3, supporting the hypothesis that the fibrils are active biological agents. Amyloid fibrils thus may provide benefit in MS and other neuroinflammatory disorders. ER -