title: Cerebral ABC transporter-common mechanisms may modulate neurodegenerative diseases and depression in elderly subjects.
abstract: In elderly subjects, depression and dementia often coincide but the actual reason is currently unknown. Does a causal link exist or is it just a reactive effect of the knowledge to suffer from dementia? The ABC transporter superfamily may represent a causal link between these mental disorders. Since the transporters ABCB1 and ABCC1 have been discovered as major β-amyloid-exporting molecules at the blood-brain barrier and ABCC1 was found to be directly activated by St. John's wort (SJW), depression and dementia certainly share an important pathophysiologic link. It was recognized that herbal anti-depressant formulations made from SJW are at least as effective for the treatment of unipolar depression in old age as classical pharmacotherapy, while having fewer side effects (Cochrane reports, 2008). SJW is known to activate various metabolizing and transport systems in the body, with cytochrome P450 enzymes and ABC transporters being most important. Does the treatment of depression in elderly subjects using pharmacological compounds or phytomedical extracts target a mechanism that also accounts for peptide storage in Alzheimer's disease and perhaps other proteopathies of the brain? In this review we summarize recent data that point to a common mechanism and present the first promising causal treatment results of demented elderly subjects with distinct SJW extracts. Insufficient trans-barrier clearance may indeed present a common problem in all the proteopathies of the brain where toxic peptides are deposited in a location-specific manner. Thus, activation of efflux molecules holds promise for future treatment of this large group of devastating disorders.
authors.affiliation: Department of Neuro-/Pathology, University of Oslo (UiO) & Oslo University Hospital (OUS), Oslo, Norway; Department of Neurology, Neurodegeneration Research Laboratory (NRL), University of Magdeburg (OvGU), Magdeburg, Germany; Leibniz Institute of Plant Biochemistry (IPB), Halle, Germany; University of Lübeck (UzL), Lübeck, Germany. Electronic address: jens.pahnke@medisin.uio.no.
authors.forename: Jens
authors.initials: J
authors.lastname: Pahnke
authors.affiliation: Department of Neurology, Neurodegeneration Research Laboratory (NRL), University of Magdeburg (OvGU), Magdeburg, Germany.
authors.forename: Christina
authors.initials: C
authors.lastname: Fröhlich
authors.affiliation: Department of Neuro-/Pathology, University of Oslo (UiO) & Oslo University Hospital (OUS), Oslo, Norway; Department of Neurology, Neurodegeneration Research Laboratory (NRL), University of Magdeburg (OvGU), Magdeburg, Germany.
authors.forename: Kristin
authors.initials: K
authors.lastname: Paarmann
authors.affiliation: Department of Neuro-/Pathology, University of Oslo (UiO) & Oslo University Hospital (OUS), Oslo, Norway; Department of Neurology, Neurodegeneration Research Laboratory (NRL), University of Magdeburg (OvGU), Magdeburg, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Krohn
authors.affiliation: Department of Geriatrics, Ullevål Hospital, University of Oslo (UiO) and Oslo University Hospital (OUS), Oslo, Norway.
authors.forename: Nenad
authors.initials: N
authors.lastname: Bogdanovic
authors.affiliation: Department NVS, Center for Alzheimer Research, Division for Neurogeriatrics, Karolinska Institutet, Stockholm, Sweden; Centre for Age-related Medicine, Stavanger University Hospital, Stavanger, Norway; Department of Neurology, Akershus University Hospital, Ahus, Norway.
authors.forename: Dag
authors.initials: D
authors.lastname: Årsland
authors.affiliation: Department NVS, Center for Alzheimer Research, Division for Neurogeriatrics, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Bengt
authors.initials: B
authors.lastname: Winblad
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000378:metabolism; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D000368:Aged; D000544:Alzheimer Disease / Q000188:drug therapy / Q000503:physiopathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D001692:Biological Transport; D001812:Blood-Brain Barrier / Q000378:metabolism*; D003863:Depression / Q000188:drug therapy / Q000503:physiopathology*; D006801:Humans; D020902:Hypericum / Q000737:chemistry; D008297:Male; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000378:metabolism*; D028321:Plant Preparations / Q000627:therapeutic use
chemical_list: D018435:ATP Binding Cassette Transporter, Subfamily B; D018528:ATP-Binding Cassette Transporters; D016229:Amyloid beta-Peptides; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D028321:Plant Preparations; C418186:ABCA2 protein, human; C513055:ABCB1 protein, human; C421109:multidrug resistance-associated protein 1
keywords: ABC transporter; Alzheimer's disease; Blood–brain barrier; Dementia; Depression; St. John's wort