title: Mitochondrial dysfunction, apoptotic cell death, and Alzheimer's disease.
abstract: Being major sources of reactive oxygen species (ROS), mitochondrial structures are exposed to high concentrations of ROS and might therefore be particularly susceptible to oxidative injury. Mitochondrial damage may play a pivotal role in the cell death decision. Bolstered evidence indicates that mitochondrial abnormalities might be part of the spectrum of chronic oxidative stress occurring in Alzheimer's disease (AD) finally contributing to synaptic failure and neuronal degeneration. Accumulation and oligomerization of amyloid beta (Abeta) is also thought to play a central role in the pathogenesis of this disease by probably directly leading to mitochondrial dysfunction. Moreover, numerous lines of findings indicate increased susceptibility to apoptotic cell death and increased oxidative damage as common features in neurons from sporadic AD patients but also from familial AD (FAD) cases. Here we provide a summary of recent work demonstrating some key abnormalities that may initiate and promote pathological events in AD. Finally, we emphasize a hypothetical sequence of the pathogenic steps linking sporadic AD, FAD, and Abeta production with mitochondrial dysfunction, caspase pathway, and neuronal loss.
authors.affiliation: Department of Pharmacology, Biocenter, J.W. Goethe University of Frankfurt, Marie-Curie-Str. 9, D-60439 Frankfurt am Main, Germany. A.Eckert@em.uni-frankfurt.de
authors.forename: Anne
authors.initials: A
authors.lastname: Eckert
authors.forename: Uta
authors.initials: U
authors.lastname: Keil
authors.forename: Celio A
authors.initials: CA
authors.lastname: Marques
authors.forename: Astrid
authors.initials: A
authors.lastname: Bonert
authors.forename: Claudia
authors.initials: C
authors.lastname: Frey
authors.forename: Katrin
authors.initials: K
authors.lastname: Schüssel
authors.forename: Walter E
authors.initials: WE
authors.lastname: Müller
mesh_terms: D000544:Alzheimer Disease / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000494:pharmacology; D017209:Apoptosis; D006801:Humans; D028361:Mitochondrial Diseases / Q000473:pathology*; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D017382:Reactive Oxygen Species