Effects of hydrated C60 fullerene on animal models of alzheimer's disease

I.Ya. Podolski1, 2, Z.A. Podlubnaya1,2, E.A. Mugantseva1, 2, E.G. Makarova1,2, L.G. Marsagishvili1, M.D. Shpagina1, O.L. Kordonets1,2, O.V. Godukhin1,2, G.V. Andrievsky3, and V.K. Klochkov3

Institute of Theoretical and Experimental Biophysics RAS, Pushchino,
Russia 2Pushchino State University, Pushchino, Russia
3Institute for Single Crystals, National Academy of Sciences of Ukraine, Ukraine

The effect of A? peptides (A?1-40 and A?1-42) is one the most important factors of pathogenesis of Alzheimer's disease (AD), a neurodegenerative disorder associated with the progressive memory impairment and dementia. Neurons and glial cells of the hippocampus and the cortex are targets for A? peptides.

The risk of AD dramatically increases in individuals beyond the age of 70. There is no effective therapy for AD. The prevention of the formation and/or the disruption of A? aggregates are the most promising approaches to the therapy of the disease.

Here we first demonstrated using transmission electron microscopy that hydrated fullerene (C60HyFn) and its small clusters strongly inhibit the formation of A? peptide fibrils in vitro. C60HyFn (1 цМ, 1 h) did not possess any toxic effect in hippocampal slices in vitro.

Our in vivo investigations in rats showed that a single intracerebroventricular injection of C60HyFn significantly improved the performance of the complicated cognitive task in normalcy and prevented the impairment of performance of the cognitive task induced by amyloid-? 25-35.

Our data allow one to suppose that unmodified fullerenes can be useful in the therapy of cognitive impairments and early stages of AD.

This study was supported by grants of the Russian Foundation for Basic Research (project no. 05-04-49331), the Program "Basic Research for Medicine" of the Presidium of the Russian Academy of Sciences, and the grant "Leading scientific schools" ( no. 4981.2006.4).