Alzheimer's Disease Research - Diagnosis, Memory Loss, Heredity, Treatment, Medication

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The ubiquitin-proteasome system in Creutzfeldt-Jakob and Alzheimer disease: intracellular redistribution of components correlates with neuronal vulnerability.

Adori C, Kovács GG, Low P, Molnár K, Gorbea C, Fellinger E, Budka H, Mayer RJ, László L

Department of General Zoology, Eötvös University of Sciences, H-1117 Budapest, Pázmány Péter sétány 1./C, Hungary.

Creutzfeldt-Jakob (CJD) and Alzheimer disease (AD) are accompanied by selective neuronal loss in the brain. We examined the regional and subcellular immunolocalization of ubiquitin, proteasomal subunits, and the heat-shock protein Hsp72 in control, CJD, and AD cases. In control and non-affected areas of disease cases, 20S proteasomes, 19S regulatory subunits, S6a, S6b, and S10b exhibit mainly cytoplasmic, whereas S4 and S7 show predominantly nuclear localization. The intensity of immunostaining for ubiquitin, proteasomal subunits, and Hsp72 varies in different anatomical regions both in disease and control brains. Areas with weaker immunolabeling correspond to affected areas in CJD and AD. In disease cases, antibodies for 20S, S4, S6b, S7, and ubiquitin intensely immunolabel neuronal nuclei of vulnerable cells in affected areas. Our results suggest that the ubiquitin-proteasome system takes part in the pathogenesis of neurodegeneration. Ubiquitin, Hsp72, and proteasomal ATPases possibly play a role in protecting certain neuronal populations in CJD and AD.

Published 18 July 2005 in Neurobiol Dis, 19(3): 427-35.
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