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.

• Authors: Michael P Kurnellas, Chris M Adams, Raymond A Sobel, Lawrence Steinman, Jonathan B Rothbard
• Journal: Science translational medicine (Sci Transl Med) Vol. 5 Issue 179 Pg. 179ra42 (Apr 03 2013) ISSN: 1946-6242 [Electronic] United States
• PMID: 23552370 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Amyloid
• Benzothiazoles
• Blood Proteins
• Interleukin-6
• Molecular Chaperones
• Peptides
• Thiazoles
• thioflavin T

Topics

• Amino Acid Sequence
• Amyloid (chemistry)
• Animals
• Benzothiazoles
• Biotinylation (drug effects)
• Blood Proteins (metabolism)
• Chemical Precipitation
• Encephalomyelitis, Autoimmune, Experimental (blood, complications, drug therapy, pathology)
• Female
• Humans
• Hydrogen-Ion Concentration
• Inflammation (blood, complications, drug therapy, pathology)
• Interleukin-6 (blood)
• Mice
• Mice, Inbred C57BL
• Molecular Chaperones (metabolism)
• Molecular Sequence Data
• Nervous System (drug effects, pathology)
• Paralysis (blood, complications, drug therapy)
• Peptides (chemistry, pharmacology, therapeutic use)
• Protein Multimerization (drug effects)
• Thiazoles (metabolism)