Effects of hydrated forms of C60 fullerene on amyloids of X-protein and A?-peptides

Z.A. Podlubnaya1, 2, I.Ya Podolski1, 2, L.G. Marsagishvili1, and M.D Shpagina1

Institute of Theoretical and Experimental Biophysics RAS, Russia 2
Pushchino State University, Pushchino, Russia

Amyloidoses are characterized by deposits of insoluble protein fibrils in different organs and tissues which arise as a result of inherited or acquired abnormality of protein folding. The search for drugs for therapy of amyloidoses is actual task. Senile plaques composed mainly by beta-amyloid (Abeta) protein are one of the pathological hallmarks of Alzheimer's disease (AD). Trying to decrease the production of Abeta is envisaged as a promising approach to prevent neurodegeneration in AD. We discovered new amyloid muscle proteins of titin family (X-, C-, H-proteins) [1] and showed their capacity to form amyloid fibrils similar to those found in the AD brain. We demonstrated also that tetracycline disrupted amyloids of the proteins and those of Abeta peptides. This confirms our idea of the possibility of similar approaches to the disruption of different amyloids due to the similarity of their physicochemical properties [1]. Here, using EM we demonstrate that under the same conditions, N6o HyFn disrupts amyloid fibrils in short protofibrils and small aggregates. We noted that N6o HyFn had the strongest anti-amyloidogenic effect on amyloids of X-protein and Abeta(25-35) peptide. The effect of N6o HyFn on Abeta(1-42) peptide was a little weaker. Probably, higher doses and/or more prolonged treatment by N6o HyFn may be required for its more effective action. Further testing of anti-amyloidogenic properties of N6o HyFn in different amyloid systems will favor the creation of new nanotechnology in therapy of amyloidoses.

The work was supported by grants RFBR 1 06-04-48896; RF Education 1.1.06; RF President «Outstanding scientific schools» * 4981.2006.4 and by RAS Presidium Program «Basic sciences for medicine» 2006.