Fourth International Symposium on Neuroacanthocytosis

Abstracts from the Fourth International Symposium on Neuroacanthocytosis

July 1-2, 2008
London and Oxford

Chairs: Prof. Kailash Bhatia, MD, FRCP, Institute of Neurology, University College London; Prof. Anthony P. Monaco, MD, PhD, Wellcome Trust Centre for Human Genetics, University of Oxford

Organizers: Antonio Velayos-Baeza, PhD; Susanne Schneider, MD; Glenn Irvine

7-2 Mitochondrial apoptosis cascade is involved in the brain pathology of ChAc-model mice
M. Matsuda, M. Nakamura, M. Ichiba, M. Kato, H. Shimo, A. Tomiyasu, N. Kono, Y. Uchinokura, S. Mori, T. Ishizuka, T. Hayashi, and A. Sano
Dept. of Psychiatry, Kagoshima University, Kagoshima, Japan

Chorea-acanthocytosis (ChAc) is a hereditary neurodegenerative disorder caused by loss of function mutations in the VPS13A gene encoding chorein. Recently, we produced a ChAc model mouse using a gene targeting technique to delete exons 60-61 that corresponds to a human disease mutation. Neuronal degeneration was observed in the striatum of the ChAc-model mouse. We performed proteomic analysis of striatal protein in the ChAc model mouse that revealed an increased protein level of DARPP-32. DARPP-32, which regulates ion channels and receptors functions acting as an inhibitor of protein phosphatase-1 (PP1) at striatum, is a pivotal integrator of dopamine signals. PP1 and protein phosphatase 2A (PP2A) dephosphorylate Bcl-2 family proteins and regulate apoptosis. We then performed immunoblot and immunohistochemical analyses to detect alterations in protein expression levels of Bcl-2 family related with apoptosis in the striatum, the cerebral cortex, and the hippocampus for comparison between wild-type and ChAc-model mice. The expression levels of PP2A and Caspase-3 tend to be increased in the striatum and the hippocampus of the ChAc-model mouse. Our preliminary results suggest that Bcl-2 family proteins are involved in the ChAc brain pathology.