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Subject: Proteasome Inhibition Causes Nigral Cell Death (AAN 2002) Date: 4/23/2002 E-MOVE reports from the 54th Annual Meeting of the American Academy of Neurology, April 13-20, in Denver Colorado. Poster numbers, session numbers, and pages are from Neurology 2002;58(supplement 7).1. Selective dopaminergic neuronal death with proteinaceous inclusions following impairment of the ubiquitin-proteasome system KSP McNaught, C Mytilineou, P Jenner, WC Olanow P05.094, A373 2. Proteasomal inhibition induces degeneration of dopaminergic neurons with inclusion bodies in the substantia nigra pars compacta of rats WC Olanow, KSP McNaught, L Bjorklund, P Jenner, O Isacson P05.095, A 374 Impairment of the proteasome leads to build-up of alpha-synuclein-positive inclusions and death of dopaminergic cells in vitro and in vivo, according to these two studies. The proteasomal inhibitor lactacystin was added to primary ventral mesencephalic cell culture, or infused unilaterally into rat substantia nigra. In both models, lactacystin produced a dose-dependent reduction in dopaminergic cells, with the appearance of proteinaceous inclusions containing alpha-synuclein. In rats, proteasome inhibition caused reduced movement which could be reversed with apomorphine. The authors conclude, "These studies support the concept that [ubiquitin-proteasome] dysfunction underlies the neuronal degeneration that occurs in PD." Proteasome activity has previously been shown to be reduced in brains of PD patients (http://www.wemove.org/emove/article.asp?ID=355). ---- 2002 E-MOVE conference reports are made possible in part through unrestricted educational grants from Elan Pharmaceuticals, Glaxo SmithKline, and Pharmacia Corporation. E-MOVE Editor: Richard Robinson, NASW, WE MOVE
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