title: Mitochondrial dysfunction--a pharmacological target in Alzheimer's disease.
abstract: Increasing evidences suggest that mitochondrial dysfunction plays an important role in the pathogenesis of neurodegenerative diseases including Alzheimer's disease (AD). Alterations of mitochondrial efficiency and function are mainly related to alterations in mitochondrial content, amount of respiratory enzymes, or changes in enzyme activities leading to oxidative stress, mitochondrial permeability transition pore opening, and enhanced apoptosis. More recently, structural changes of the network are related to bioenergetic function, and its consequences are a matter of intensive research. Several mitochondria-targeting compounds with potential efficacy in AD including dimebon, methylene blue, piracetam, simvastatin, Ginkgo biloba, curcumin, and omega-3 polyunsaturated fatty acids have been identified. The majority of preclinical data indicate beneficial effects, whereas most controlled clinical trials did not meet the expectations. Since mitochondrial dysfunction represents an early event in disease progression, one reason for the disappointing clinical results could be that pharmacological interventions might came too late. Thus, more studies are needed that focus on therapeutic strategies starting before severe disease progress.
authors.affiliation: Department of Pharmacology, Biocenter, Campus Riedberg, Goethe-University, Biocentre Geb. N260, R.1.09, Max-von-Laue Str. 9, 60438 Frankfurt, Germany. g.p.eckert@em.uni-frankfurt.de
authors.forename: Gunter P
authors.initials: GP
authors.lastname: Eckert
authors.forename: Kathrin
authors.initials: K
authors.lastname: Renner
authors.forename: Schamim H
authors.initials: SH
authors.lastname: Eckert
authors.forename: Janett
authors.initials: J
authors.lastname: Eckmann
authors.forename: Stephanie
authors.initials: S
authors.lastname: Hagl
authors.forename: Reham M
authors.initials: RM
authors.lastname: Abdel-Kader
authors.forename: Christopher
authors.initials: C
authors.lastname: Kurz
authors.forename: Kristina
authors.initials: K
authors.lastname: Leuner
authors.forename: Walter E
authors.initials: WE
authors.lastname: Muller
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy / Q000473:pathology* / Q000503:physiopathology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001688:Biological Products / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D033681:Mitochondrial Membrane Transport Proteins / Q000378:metabolism; D000083162:Mitochondrial Permeability Transition Pore; D018384:Oxidative Stress / Q000187:drug effects
chemical_list: D001688:Biological Products; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore