Subject: PD: Molecular Physiology and Pathophysiology (AAN 2000)
Date: 5/10/2000E-MOVE reports from the 52nd Annual Meeting of the American Academy of Neurology, held in San Diego, California, 30 April-5 May 2000. Citation numbers below refer to abstracts of presentations and posters, which are published in Neurology 2000;54(suppl.3).
1.Epstein-Barr virus latent membrane protein immunoreactivity in Lewy bodies: An example of molecular mimicry between EBV and alpha-synuclein
JM Woulfe, DG Munoz
An antibody against Epstein-Barr virus reacts with alpha-synuclein, according to this study.
A monoclonal antibody was generated against Epstein-Barr virus latent membrane protein (EBV- LMP). Immunohistochemical analysis of antibody-protein interaction in normal brain showed "identical topographic and cellular patterns of distribution in all areas examined" for both the EBV-LMP antibody and other alpha-synuclein markers. Within Lewy bodies in PD brain, the pattern of distribution matched that of alpha-synuclein, but not ubiquitin, tau, or neurofilament protein. Direct interaction of the antibody with alpha-synuclein was confirmed by western blot and ELISA. The authors conclude, "Assuming that similar antibodies are generated during natural latent infection with EBV, these results could bear implications with respect to elucidating a virally initiated, autoimmune pathogenesis for Parkinson's disease, and, perhaps, for other ‘alpha- synucleinopathies.'"
2. Gene microarray analysis of Parkinson's disease specimens
MV Karpuj, P Chan, D Di Monte, JW Langston, L Steinman
Messenger RNA from the putamen of PD brain was compared to that from normal putamen using gene microarray analysis, which uses DNA chip technology to analyze whole-cell gene expression. The largest increases in gene expression in PD brain were for metallothioneins, apolipoprotein D and E, cytochrome P450, Fas/Apo 1 (an apoptosis-related gene), cytochrome oxidase VIIa, and beta-4 nicotinic acetylcholine receptor. Comparison of expression in PD vs. HD showed elevation in PD, but decrease in HD, of cytochrome P450, proteasome subunits 40 and p55, nitric oxide synthase, cholecystokinin receptor, and ubiquitin conjugating enzyme UCh5.
3. Parkin is associated with actin filaments of neuronal and nonneural cells
DP Huynh, DR Scoles, M Del Bigio, SM Pulst
Polyclonal antibodies to parkin, the protein responsible for autosomal recessive juvenile-onset parkinsonism, were used to examine distribution of parkin in normal and diseased tissue. Parkin was found in both neural and nonneural tissue, and colocalized with actin fibers in neuronal processes in the basal ganglia and parts of the cerebellum. It was not found in high concentration in neuronal cell bodies, and was absent from Lewy bodies.
Other recent findings on parkin distribution can be found at http://www.wemove.org/emove/article.asp?ID=186
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