title: Impaired mitochondrial energy production and ABC transporter function-A crucial interconnection in dementing proteopathies of the brain.
abstract: Ageing is the main risk factor for the development of dementing neurodegenerative diseases (NDs) and it is accompanied by the accumulation of variations in mitochondrial DNA. The resulting tissue-specific alterations in ATP production and availability cause deteriorations of cerebral clearance mechanisms that are important for the removal of toxic peptides and its aggregates. ABC transporters were shown to be the most important exporter superfamily for toxic peptides, e.g. β-amyloid and α-synuclein. Their activity is highly dependent on the availability of ATP and forms a directed energy-exporter network, linking decreased mitochondrial function with highly impaired ABC transporter activity and disease progression. In this paper, we describe a network based on interactions between ageing, energy metabolism, regeneration, accumulation of toxic peptides and the development of proteopathies of the brain with a focus on Alzheimer's disease (AD). Additionally, we provide new experimental evidence for interactions within this network in regenerative processes in AD.
authors.affiliation: Neurodegeneration Research Lab (NRL), Department of Neurology, University of Magdeburg, Leipziger Str. 44, H64, 39120 Magdeburg, Germany; German Center for Neurodegenerative Diseases (DZNE) Magdeburg, Leipziger Str. 44, H64, 39120 Magdeburg, Germany. Electronic address: jens.pahnke@gmail.com.
authors.forename: Jens
authors.initials: J
authors.lastname: Pahnke
authors.forename: Christina
authors.initials: C
authors.lastname: Fröhlich
authors.forename: Markus
authors.initials: M
authors.lastname: Krohn
authors.forename: Toni
authors.initials: T
authors.lastname: Schumacher
authors.forename: Kristin
authors.initials: K
authors.lastname: Paarmann
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism*; D000375:Aging / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D004734:Energy Metabolism / Q000235:genetics; D006801:Humans; D051379:Mice; D051844:alpha-Synuclein / Q000235:genetics / Q000378:metabolism
chemical_list: D018528:ATP-Binding Cassette Transporters; D016229:Amyloid beta-Peptides; D051844:alpha-Synuclein
keywords: ABC transporters; ABCA1; ABCA7; ABCB1; ABCC1; Ageing; Alzheimer's disease; Aqp4; Dementia; Energy metabolism; Mitochondria; Neurodegeneration; Parkinson's disease