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  Chaperones increase association of tau protein with microtubules

Dou, F., Netzer, W. J., Tanemura, K., Li, F., Hartl, F. U., Takashima, A., et al. (2003). Chaperones increase association of tau protein with microtubules. Proceedings of the National Academy of Sciences of the United States of America, 100(2), 721-726.

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Genre: Journal Article
Alternative Title : Proc. Natl. Acad. Sci. U. S. A.

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 Creators:
Dou, F., Author
Netzer, W. J., Author
Tanemura, K., Author
Li, F., Author
Hartl, F. U.1, Author              
Takashima, A., Author
Gouras, G. K., Author
Greengard, P., Author
Xu, H. X., Author
Affiliations:
1Hartl, Franz-Ulrich / Cellular Biochemistry, Max Planck Institute of Biochemistry, Max Planck Society, ou_1565152              

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 Abstract: Molecular chaperones and their functions in protein folding have been implicated in several neurodegenerative diseases, including Parkinson's disease and Huntington's disease, which are characterized by accumulation of protein aggregates (e.g., alpha-synuclein and huntingtin, respectively). These aggregates have been shown in various experimental systems to respond to changes in levels of molecular chaperones suggesting the possibility of therapeutic intervention and a role for chaperones in disease pathogenesis. It remains unclear whether chaperones also play a role in Alzheimer's disease, a neurodegenerative disorder characterized by beta-amyloid and tau protein aggregates. Here, we report an inverse relationship between aggregated tau and the levels of heat shock protein (Hsp)70/90 in tau transgenic mouse and Alzheimer's disease brains. In various cellular models, increased levels of Hsp70 and Hsp90 promote tau solubility and tau binding to microtubules, reduce insoluble tau and cause reduced tau phosphorylation. Conversely, lowered levels of Hsp70 and Hsp90 result in the opposite effects. We have also demonstrated a direct association of the chaperones with tau proteins. Our results suggest that up-regulation of molecular chaperones may suppress formation of neurofibrillary tangles by partitioning tau into a productive folding pathway and thereby preventing tau aggregation.

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Language(s): eng - English
 Dates: 2003-01-21
 Publication Status: Published in print
 Pages: -
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 Table of Contents: -
 Rev. Type: Peer
 Identifiers: eDoc: 41663
ISI: 000180589000062
 Degree: -

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Title: Proceedings of the National Academy of Sciences of the United States of America
  Alternative Title : Proc. Natl. Acad. Sci. U. S. A.
Source Genre: Journal
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Affiliations:
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Pages: - Volume / Issue: 100 (2) Sequence Number: - Start / End Page: 721 - 726 Identifier: ISSN: 0027-8424