QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, October 1, 2003, 23(26):8872-8880

This Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (32) Citing Articles via Google Scholar Google Scholar Articles by Goldbaum, O. Articles by Richter-Landsberg, C. Search for Related Content PubMed PubMed Citation Articles by Goldbaum, O. Articles by Richter-Landsberg, C.

 Previous Article  |  Next Article 

Cellular/Molecular
Proteasome Inhibition Stabilizes Tau Inclusions in Oligodendroglial Cells that Occur after Treatment with Okadaic Acid

Olaf Goldbaum,¹ Malte Oppermann,¹ Melanie Handschuh,¹ Deepa Dabir,² Bin Zhang,² Mark S. Forman,² John Q. Trojanowski,^2,3 Virginia M.-Y. Lee,² and Christiane Richter-Landsberg¹

¹University of Oldenburg, Department of Biology, Molecular Neurobiology, D-26111 Oldenburg, Germany, and ²Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, and ³Institute on Aging, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104

Tau-positive inclusions in oligodendrocytes are consistent neuropathological features of corticobasal degeneration, progressive supranuclear palsy, and frontotemporal dementias with Parkinsonism linked to chromosome 17. Here we show by immunohistochemistry that tau-positive oligodendroglial inclusion bodies also contain the small heat-shock protein (HSP) B-crystallin but not HSP70. To study the molecular mechanisms underlying inclusion body formation, we engineered an oligodendroglia cell line (OLN-t40) to overexpress the longest human tau isoform. Treatment of OLN-t40 cells with okadaic acid (OA), an inhibitor of protein phosphatase 2A, caused tau hyperphosphorylation and a decrease in the binding of tau to microtubules. Simultaneously, tau-positive aggregates that also stained with the amyloid-binding dye thioflavin-S as well as with antibodies to tau and B-crystallin were detected. However, they were only transiently expressed and were degraded within 24 hr. When the proteasomal apparatus was inhibited by carbobenzoxy-L-leucyl-L-leucyl-L-leucinal (MG-132) after OA treatment, the aggregates were stabilized and were still detectable after 18 hr in the absence of OA. Incubation with MG-132 alone inhibited tau proteolysis and led to the induction of HSPs, including B-crystallin and to its translocation to the perinuclear region, but did not induce the formation of thioflavin-S-positive aggregates. Hence, although tau hyperphosphorylation induced by protein phosphatase inhibition contributes to pathological aggregate formation, only hyperphosporylation of tau followed by proteasome inhibition leads to stable fibrillary deposits of tau similar to those observed in neurodegenerative diseases.

Key words: B-crystallin; cytoskeleton; tau phosphorylation; coiled bodies; glial inclusions; proteasome; thioflavin-S

---

Received June 19, 2003; revised August 5, 2003; accepted August 12, 2003.

This article has been cited by other articles:

				J. M.M. Tan, E. S.P. Wong, D. S. Kirkpatrick, O. Pletnikova, H. S. Ko, S.-P. Tay, M. W.L. Ho, J. Troncoso, S. P. Gygi, M. K. Lee, et al. Lysine 63-linked ubiquitination promotes the formation and autophagic clearance of protein inclusions associated with neurodegenerative diseases Hum. Mol. Genet., February 1, 2008; 17(3): 431 - 439. [Abstract] [Full Text] [PDF]

				Y.-J. Zhang, Y.-F. Xu, Y.-H. Liu, J. Yin, H.-L. Li, Q. Wang, and J.-Z. Wang Peroxynitrite induces Alzheimer-like tau modifications and accumulation in rat brain and its underlying mechanisms FASEB J, July 1, 2006; 20(9): 1431 - 1442. [Abstract] [Full Text] [PDF]

				A. d. C. Alonso, B. Li, I. Grundke-Iqbal, and K. Iqbal Polymerization of hyperphosphorylated tau into filaments eliminates its inhibitory activity PNAS, June 6, 2006; 103(23): 8864 - 8869. [Abstract] [Full Text] [PDF]

				K. Uryu, C. Richter-Landsberg, W. Welch, E. Sun, O. Goldbaum, E. H. Norris, C.-T. Pham, I. Yazawa, K. Hilburger, M. Micsenyi, et al. Convergence of Heat Shock Protein 90 with Ubiquitin in Filamentous {alpha}-Synuclein Inclusions of {alpha}-Synucleinopathies Am. J. Pathol., March 1, 2006; 168(3): 947 - 961. [Abstract] [Full Text] [PDF]

				A. d. C. Alonso, A. Mederlyova, M. Novak, I. Grundke-Iqbal, and K. Iqbal Promotion of Hyperphosphorylation by Frontotemporal Dementia Tau Mutations J. Biol. Chem., August 13, 2004; 279(33): 34873 - 34881. [Abstract] [Full Text] [PDF]

				O. Goldbaum and C. Richter-Landsberg Proteolytic Stress Causes Heat Shock Protein Induction, Tau Ubiquitination, and the Recruitment of Ubiquitin to Tau-Positive Aggregates in Oligodendrocytes in Culture J. Neurosci., June 23, 2004; 24(25): 5748 - 5757. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help