WWW.JNEUROSCI.ORG
-
The Journal of Neuroscience
QUICK SEARCH:   [advanced]


     
-


HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP
The Journal of Neuroscience, March 14, 2007, 27(11):2896-2907; doi:10.1523/JNEUROSCI.4674-06.2007

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow A correction has been published
Right arrow Submit an eLetter
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Web of Science (35)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Thies, E.
Right arrow Articles by Mandelkow, E.-M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Thies, E.
Right arrow Articles by Mandelkow, E.-M.

 Previous Article  |  Next Article 

Neurobiology of Disease
Missorting of Tau in Neurons Causes Degeneration of Synapses That Can Be Rescued by the Kinase MARK2/Par-1

Edda Thies and Eva-Maria Mandelkow

Max-Planck-Unit for Structural Molecular Biology, 22607 Hamburg, Germany

Correspondence should be addressed to Dr. Eva-Maria Mandelkow, Max-Planck-Unit for Structural Molecular Biology, Notkestrasse 85, 22607 Hamburg, Germany. Email: mandelkow{at}mpasmb.desy.de

Early hallmarks of Alzheimer's disease include the loss of synapses, which precedes the loss of neurons and the pathological phosphorylation and aggregation of tau protein. Mitochondrial dysfunction has been suggested as a reason, but evidence on the role of tau was lacking. Here, we show that transfection of tau in mature hippocampal neurons leads to an improper distribution of tau into the somatodendritic compartment with concomitant degeneration of synapses, as seen by the disappearance of spines and of presynaptic and postsynaptic markers. This is accompanied by transport inhibition of vesicles and organelles, concomitant with an increase and bundling of microtubules. Mitochondria degenerate, thus causing ATP levels to decrease. The tau-induced synaptic decay can be relieved by the activation of the kinase MARK2 (microtubule-associated protein/microtubule affinity regulating kinase 2)/Par-1 (protease-activated receptor 1), which can remove tau from the microtubule tracks and reverses the transport block. This leads to the rescue of dendritic spines, synapses, mitochondrial transport and ATP levels.

Key words: Alzheimer's disease; axonal traffic; microtubules; mitochondria; neurons; synapses; tau

Received Oct. 27, 2006; revised Jan. 30, 2007; accepted Feb. 2, 2007.

Correspondence should be addressed to Dr. Eva-Maria Mandelkow, Max-Planck-Unit for Structural Molecular Biology, Notkestrasse 85, 22607 Hamburg, Germany. Email: mandelkow{at}mpasmb.desy.de




This article has been cited by other articles:


Home page
 J. Biol. Chem.Home page
T. Timm, K. Balusamy, X. Li, J. Biernat, E. Mandelkow, and E.-M. Mandelkow
Glycogen Synthase Kinase (GSK) 3{beta} Directly Phosphorylates Serine 212 in the Regulatory Loop and Inhibits Microtubule Affinity-regulating Kinase (MARK) 2
J. Biol. Chem., July 4, 2008; 283(27): 18873 - 18882.
[Abstract] [Full Text] [PDF]

Home page
 FASEB J.Home page
A. Deshpande, K. M. Win, and J. Busciglio
Tau isoform expression and regulation in human cortical neurons
FASEB J, July 1, 2008; 22(7): 2357 - 2367.
[Abstract] [Full Text] [PDF]

Home page
 BrainHome page
M. D. Ikonomovic, W. E. Klunk, E. E. Abrahamson, C. A. Mathis, J. C. Price, N. D. Tsopelas, B. J. Lopresti, S. Ziolko, W. Bi, W. R. Paljug, et al.
Post-mortem correlates of in vivo PiB-PET amyloid imaging in a typical case of Alzheimer's disease
Brain, June 1, 2008; 131(6): 1630 - 1645.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Biol. CellHome page
C. Johne, D. Matenia, X.-y. Li, T. Timm, K. Balusamy, and E.-M. Mandelkow
Spred1 and TESK1--Two New Interaction Partners of the Kinase MARKK/TAO1 That Link the Microtubule and Actin Cytoskeleton
Mol. Biol. Cell, April 1, 2008; 19(4): 1391 - 1403.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
M.-M. Mocanu, A. Nissen, K. Eckermann, I. Khlistunova, J. Biernat, D. Drexler, O. Petrova, K. Schonig, H. Bujard, E. Mandelkow, et al.
The Potential for -Structure in the Repeat Domain of Tau Protein Determines Aggregation, Synaptic Decay, Neuronal Loss, and Coassembly with Endogenous Tau in Inducible Mouse Models of Tauopathy
J. Neurosci., January 16, 2008; 28(3): 737 - 748.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
E. Elliott, P. Tsvetkov, and I. Ginzburg
BAG-1 Associates with Hsc70{middle dot}Tau Complex and Regulates the Proteasomal Degradation of Tau Protein
J. Biol. Chem., December 21, 2007; 282(51): 37276 - 37284.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
K. Eckermann, M.-M. Mocanu, I. Khlistunova, J. Biernat, A. Nissen, A. Hofmann, K. Schonig, H. Bujard, A. Haemisch, E. Mandelkow, et al.
The beta-Propensity of Tau Determines Aggregation and Synaptic Loss in Inducible Mouse Models of Tauopathy
J. Biol. Chem., October 26, 2007; 282(43): 31755 - 31765.
[Abstract] [Full Text] [PDF]


-
-

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help
-
Copyright 2009 by Society for Neuroscience ONLINE ISSN: 1529-2401
-