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Antioxidants & Redox Signaling
Mitochondrial Dysfunction: The First Domino in Brain Aging and Alzheimer's Disease?

To cite this article:
Kristina Leuner, Susanne Hauptmann, Reham Abdel-Kader, Isabel Scherping, Uta Keil, Johanna B. Strosznajder, Anne Eckert, Walter E. Müller. Antioxidants & Redox Signaling. October 2007, 9(10): 1659-1676. doi:10.1089/ars.2007.1763.

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Kristina Leuner 
Department of Pharmacology, Zafes, Biocenter, University of Frankfurt, Germany.
Susanne Hauptmann 
Department of Pharmacology, Zafes, Biocenter, University of Frankfurt, Germany.
Reham Abdel-Kader 
Department of Pharmacology, Zafes, Biocenter, University of Frankfurt, Germany.
Isabel Scherping 
Department of Pharmacology, Zafes, Biocenter, University of Frankfurt, Germany.
Uta Keil 
Department of Pharmacology, Zafes, Biocenter, University of Frankfurt, Germany.
Johanna B. Strosznajder 
Department of Cellular Signalling, Polish Academy of Science, Warzawa, Poland.
Anne Eckert 
Neurobiology Research Laboratory, Psychiatric University Clinic, Basel, Switzerland.
Walter E. Müller 
Department of Pharmacology, Zafes, Biocenter, University of Frankfurt, Germany.

With the increasing average life span of humans and with decreasing cognitive function in elderly individuals, age-related cognitive disorders including dementia have become a major health problem in society. Aging-related mitochondrial dysfunction underlies many common neurodegenerative disorders diseases, including Alzheimer's disease (AD). AD is characterized by two major histopathological hallmarks, initially intracellular and with the progression of the disease extracellular accumulation of oligomeric and fibrillar β-amyloid (Aβ) peptides and intracellular neurofibrillary tangles (NFT) composed of hyperphosphorylated tau protein. In this review, the authors focus on the latest findings in AD animal models indicating that these histopathological alterations induce deficits in the function of the complexes of the respiratory chain and therefore consecutively result in mitochondrial dysfunction. This parameter is intrinsically tied to oxidative stress. Both are early events in aging and especially in the pathogenesis of aging-related severe neurodegeneration. Ginkgo biloba extract seems to be of therapeutic benefit in the treatment of mild to moderate dementia of different etiology, although the data are quite heterogeneous. Herein, the authors suggest that mitochondrial protection and subsequent reduction of oxidative stress are important components of the neuroprotective activity of Ginkgo biloba extract.

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