Amyloid fibrils composed of hexameric peptides attenuate neuroinflammation

MP Kurnellas, CM Adams, RA Sobel… - Science translational …, 2013 - science.org
MP Kurnellas, CM Adams, RA Sobel, L Steinman, JB Rothbard
Science translational medicine, 2013science.org
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 …
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.
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