Insights into mitochondrial dysfunction: aging, amyloid-β, and tau-A deleterious trio

Schmitt, Karen, Grimm, Amandine, Kazmierczak, Anna, Strosznajder, Joanna B., Gotz, Jurgen and Eckert, Anne (2012) Insights into mitochondrial dysfunction: aging, amyloid-β, and tau-A deleterious trio. Antioxidants and Redox Signaling, 16 12: 1456-1466. doi:10.1089/ars.2011.4400

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Author Schmitt, Karen
Grimm, Amandine
Kazmierczak, Anna
Strosznajder, Joanna B.
Gotz, Jurgen
Eckert, Anne
Title Insights into mitochondrial dysfunction: aging, amyloid-β, and tau-A deleterious trio
Journal name Antioxidants and Redox Signaling   Check publisher's open access policy
ISSN 1523-0864
Publication date 2012-04-19
Year available 2012
Sub-type Critical review of research, literature review, critical commentary
DOI 10.1089/ars.2011.4400
Open Access Status File (Author Post-print)
Volume 16
Issue 12
Start page 1456
End page 1466
Total pages 11
Place of publication New Rochelle, NY, United States
Publisher Mary Ann Liebert
Language eng
Subject 1303 Specialist Studies in Education
1307 Cell Biology
1312 Molecular Biology
1314 Physiology
1308 Clinical Biochemistry
Abstract Significance: Alzheimer's disease (AD) is an age-related progressive neurodegenerative disorder mainly affecting elderly individuals. The pathology of AD is characterized by amyloid plaques (aggregates of amyloid-β [Aβ]) and neurofibrillary tangles (aggregates of tau), but the mechanisms underlying this dysfunction are still partially unclear. Recent Advances: A growing body of evidence supports mitochondrial dysfunction as a prominent and early, chronic oxidative stress-associated event that contributes to synaptic abnormalities and, ultimately, selective neuronal degeneration in AD. Critical Issues: In this review, we discuss on the one hand whether mitochondrial decline observed in brain aging is a determinant event in the onset of AD and on the other hand the close interrelationship of this organelle with Aβ and tau in the pathogenic process underlying AD. Moreover, we summarize evidence from aging and Alzheimer models showing that the harmful trio "aging, Aβ, and tau protein" triggers mitochondrial dysfunction through a number of pathways, such as impairment of oxidative phosphorylation (OXPHOS), elevation of reactive oxygen species production, and interaction with mitochondrial proteins, contributing to the development and progression of the disease. Future Directions: The aging process may weaken the mitochondrial OXPHOS system in a more general way over many years providing a basis for the specific and destructive effects of Aβ and tau. Establishing strategies involving efforts to protect cells at the mitochondrial level by stabilizing or restoring mitochondrial function and energy homeostasis appears to be challenging, but very promising route on the horizon.
Keyword Biochemistry & Molecular Biology
Endocrinology & Metabolism
Biochemistry & Molecular Biology
Endocrinology & Metabolism
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID 31000_122572
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Critical review of research, literature review, critical commentary
Collection: Queensland Brain Institute Publications
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Citation counts: TR Web of Science Citation Count  Cited 64 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 72 times in Scopus Article | Citations
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