[Research Articles] Amyloid Fibrils Composed of Hexameric Peptides Attenuate Neuroinflammation

Sci Transl Med 3 April 2013:
Vol. 5, Issue 179, p. 179ra42
Sci. Transl. Med. DOI: 10.1126/scitranslmed.3005681 Multiple Sclerosis Michael P. Kurnellas1, Chris M. Adams2, Raymond A. Sobel3, Lawrence Steinman1,* and Jonathan B. Rothbard1,4

1Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA 94305–5316, USA.

2Stanford University Mass Spectrometry, Stanford University School of Medicine, Stanford, CA 94305–5316, USA.

3Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305–5316, USA.

4Division of Immunology and Rheumatology, Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305–5316, USA. ?*Corresponding author. E-mail: steinman{at}stanford.eduThe amyloid-forming proteins tau, aB 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 aB crystallin (HspB5) and from amyloid ß 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 ß 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.

Copyright © 2013, American Association for the Advancement of ScienceCitation: M. P. Kurnellas, C. M. Adams, R. A. Sobel, L. Steinman, J. B. Rothbard, Amyloid Fibrils Composed of Hexameric Peptides Attenuate Neuroinflammation. Sci. Transl. Med. 5, 179ra42 (2013).

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