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Vice versa, as demonstrated in this study, treatment of pheochromocytoma (PC12) cells with nerve growth factor (NGF) or other differentiating agents reduces proteasomal activity. This is accompanied by an increase in mRNA and protein levels of the catalytically active subunits \u03b21, \u03b22 and \u03b25, but not of their inducible counterparts, indicating changes in subunit composition of the proteasome during neuronal differentiation. In contrast to neuronal cell lines, however, pre\u2010treatment of primary neurons with proteasome inhibitors completely prevents axon formation, and lower concentrations of lactacystin (0.5\u20135\u2003\u00b5<jats:sc>m<\/jats:sc>) significantly reduce axonal elongation and branching <jats:italic>in vitro<\/jats:italic>. Furthermore, established axonal networks degenerate rapidly and long\u2010term survival of peripheral neurons is impaired in the presence of proteasome inhibitors. Axonal pathology is reminiscent of the morphological changes observed in neurodegenerative disorders and supports a crucial role of the constitutive catalytic subunits in axon initiation, maintenance and regeneration.<\/jats:p>","DOI":"10.1111\/j.1471-4159.2006.03694.x","type":"journal-article","created":{"date-parts":[[2006,9,14]],"date-time":"2006-09-14T16:28:14Z","timestamp":1158251294000},"page":"1708-1717","source":"Crossref","is-referenced-by-count":25,"title":["Constitutively expressed catalytic proteasomal subunits are up\u2010regulated during neuronal differentiation and required for axon initiation, elongation and maintenance"],"prefix":"10.1111","volume":"96","author":[{"given":"Lars","family":"Klimaschewski","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Barbara","family":"Hausott","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shota","family":"Ingorokva","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kristian","family":"Pfaller","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2006,3,3]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.97.19.10424"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biophys.28.1.295"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1078\/0171-9335-00362"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-04-0338"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0166-2236(02)02255-5"},{"key":"e_1_2_7_7_1","doi-asserted-by":"crossref","first-page":"11\u2003653","DOI":"10.1523\/JNEUROSCI.23-37-11653.2003","article-title":"Neuronal induction of the immunoproteasome in Huntington's disease","volume":"23","author":"Diaz\u2010Hernandez M.","year":"2003","journal-title":"J. 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