March separate, strike together: role of phosphorylated TAU in mitochondrial dysfunction in Alzheimer's disease

Eckert, Anne, Nisbet, Rebecca, Grimm, Amandine and Götz, Jürgen (2013) March separate, strike together: role of phosphorylated TAU in mitochondrial dysfunction in Alzheimer's disease. Biochimica et Biophysica Acta (BBA): Molecular Basis of Disease, 1842 8: 1258-1266. doi:10.1016/j.bbadis.2013.08.013

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Author Eckert, Anne
Nisbet, Rebecca
Grimm, Amandine
Götz, Jürgen
Title March separate, strike together: role of phosphorylated TAU in mitochondrial dysfunction in Alzheimer's disease
Journal name Biochimica et Biophysica Acta (BBA): Molecular Basis of Disease   Check publisher's open access policy
ISSN 0925-4439
Publication date 2013-09-17
Year available 2013
Sub-type Critical review of research, literature review, critical commentary
DOI 10.1016/j.bbadis.2013.08.013
Open Access Status Not Open Access
Volume 1842
Issue 8
Start page 1258
End page 1266
Total pages 9
Place of publication Amsterdam, Netherlands
Publisher Elsevier
Language eng
Formatted abstract
Highlights
• TAU and Abeta separately and synergistically impair mitochondrial functions.
• Suitable animal models are the SAMP and Harlequin strains and TAU transgenic mice.
• TAU specifically impairs complex I and Abeta complex IV.
• TAU impairs mitochondrial transport.
• TAU impairs mitochondrial dynamics favouring mitochondrial elongation.

The energy demand and calcium buffering requirements of the brain are met by the high number of mitochondria in neurons and in these, especially at the synapses. Mitochondria are the major producer of reactive oxygen species (ROS); at the same time, they are damaged by ROS that are induced by abnormal protein aggregates that characterize human neurodegenerative diseases such as Alzheimer's disease (AD). Because synaptic mitochondria are long-lived, any damage exerted by these aggregates impacts severely on neuronal function. Here we review how increased TAU, a defining feature of AD and related tauopathies, impairs mitochondrial function by following the principle: ‘March separate, strike together!’ In the presence of amyloid-β, TAU's toxicity is augmented suggesting synergistic pathomechanisms. In order to restore mitochondrial functions in neurodegeneration as a means of therapeutic intervention it will be important to integrate the various aspects of dysfunction and get a handle on targeting distinct cell types and subcellular compartments.

This article is part of a Special Issue entitled: Misfolded Proteins, Mitochondrial Dysfunction and Neurodegenerative Diseases.
Keyword Alzheimer's disease
Axonal transport
DRP1
Mitochondrion
Tauopathy
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Available online 17 September 2013

Document type: Journal Article
Sub-type: Critical review of research, literature review, critical commentary
Collections: Queensland Brain Institute Publications
Official 2014 Collection
 
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Citation counts: TR Web of Science Citation Count  Cited 22 times in Thomson Reuters Web of Science Article | Citations
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Created: Thu, 06 Mar 2014, 23:40:03 EST by Rebecca Nisbet on behalf of Clem Jones Centre for Ageing Dementia Research