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-crystallin, prevents A
fibril formation and toxicity
1 Department of Chemical Engineering, Texas A&M University, College Station, Texas 77843–3122, USA
2 Department of Medical Biochemistry and Genetics, Texas A&M University System Health Science Center, College Station, Texas 77845–1114, USA
3 Department of Chemical and Biochemical Engineering, The University of Maryland, Baltimore County (UMBC), Baltimore, Maryland 21250, USA
(RECEIVED August 31, 2004; FINAL REVISION November 9, 2004; ACCEPTED November 10, 2004)
-Amyloid (A) is a major protein component of senile plaques in Alzheimer’s disease, and is neurotoxic when aggregated. The size of aggregated A responsible for the observed neurotoxicity and the mechanism of aggregation are still under investigation; however, prevention of A aggregation still holds promise as a means to reduce A neurotoxicity. In research presented here, we show that Hsp20, a novel 
-crystallin isolated from the bovine erythrocyte parasite Babesia bovis, was able to prevent aggregation of denatured alcohol dehydrogenase when the two proteins are present at near equimolar levels. We then examined the ability of Hsp20 produced as two different fusion proteins to prevent A amyloid formation as indicated by Congo Red binding; we found that not only was Hsp20 able to dramatically reduce Congo Red binding, but it was able to do so at molar ratios of Hsp20 to A of 1 to 1000. Electron microscopy confirmed that Hsp20 does prevent A fibril formation. Hsp20 was also able to significantly reduce A toxicity to both SH-SY5Y and PC12 neuronal cells at similar molar ratios. At high concentrations of Hsp20, the protein no longer displays its aggregation inhibition and toxicity attenuation properties. Size exclusion chromatography indicated that Hsp20 was active at low concentrations in which dimer was present. Loss of activity at high concentrations was associated with the presence of higher oligomers of Hsp20. This work could contribute to the development of a novel aggregation inhibitor for prevention of A toxicity.
Keywords: Alzheimer’s disease; protein folding; chaperone; amyloid; aggregation
Article and publication date are at http://www.proteinscience.org/cgi/doi/10.1110/ps.041020705.
Reprint requests to: Theresa Good, Chemical and Biochemical Engineering, UMBC,1000 Hilltop Circle, Baltimore, MD 21250, USA; e-mail: tgood{at}umbc.edu; fax: (410) 455-1049.
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