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Amyloid fibrils composed of hexameric peptides attenuate neuroinflammation.

Abstract：

: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.

journal_name

Sci Transl Med

journal_title

Science translational medicine

authors

Kurnellas MP,Adams CM,Sobel RA,Steinman L,Rothbard JB

doi

10.1126/scitranslmed.3005681

subject

Has Abstract

pub_date

2013-04-03 00:00:00

pages

179ra42

issue

179

eissn

1946-6234

issn

1946-6242

pii

5/179/179ra42

journal_volume

5

pub_type

杂志文章

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