title: Astrocytic transporters in Alzheimer's disease.
abstract: Astrocytes play a fundamental role in maintaining the health and function of the central nervous system. Increasing evidence indicates that astrocytes undergo both cellular and molecular changes at an early stage in neurological diseases, including Alzheimer's disease (AD). These changes may reflect a change from a neuroprotective to a neurotoxic phenotype. Given the lack of current disease-modifying therapies for AD, astrocytes have become an interesting and viable target for therapeutic intervention. The astrocyte transport system covers a diverse array of proteins involved in metabolic support, neurotransmission and synaptic architecture. Therefore, specific targeting of individual transporter families has the potential to suppress neurodegeneration, a characteristic hallmark of AD. A small number of the 400 transporter superfamilies are expressed in astrocytes, with evidence highlighting a fraction of these are implicated in AD. Here, we review the current evidence for six astrocytic transporter subfamilies involved in AD, as reported in both animal and human studies. This review confirms that astrocytes are indeed a viable target, highlights the complexities of studying astrocytes and provides future directives to exploit the potential of astrocytes in tackling AD.
authors.affiliation: Department of Biology, University of York, Heslington, York YO10 5DD, U.K.
authors.forename: Chris
authors.initials: C
authors.lastname: Ugbode
authors.affiliation: School of Pharmacy, University of Reading, Reading RG6 6UB, U.K.
authors.forename: Yuhan
authors.initials: Y
authors.lastname: Hu
authors.affiliation: School of Pharmacy, University of Reading, Reading RG6 6UB, U.K.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Whalley
authors.affiliation: School of Medicine, University of Leeds, Leeds LS2 9JT, U.K.
authors.forename: Chris
authors.initials: C
authors.lastname: Peers
authors.affiliation: School of Pharmacy, University of Bradford, Bradford BD7 1DP, U.K.
authors.forename: Marcus
authors.initials: M
authors.lastname: Rattray
authors.affiliation: School of Pharmacy, University of Reading, Reading RG6 6UB, U.K.
authors.forename: Mark L
authors.initials: ML
authors.lastname: Dallas
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism; D000544:Alzheimer Disease / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D001253:Astrocytes / Q000378:metabolism* / Q000473:pathology; D050485:GABA Plasma Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D051246:Glucose Transport Proteins, Facilitative / Q000235:genetics / Q000378:metabolism; D050491:Glutamate Plasma Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D050487:Glycine Plasma Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D026901:Membrane Transport Proteins / Q000235:genetics* / Q000378:metabolism; D005810:Multigene Family; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D000254:Sodium-Potassium-Exchanging ATPase / Q000235:genetics / Q000378:metabolism
chemical_list: D018528:ATP-Binding Cassette Transporters; D050485:GABA Plasma Membrane Transport Proteins; D051246:Glucose Transport Proteins, Facilitative; D050491:Glutamate Plasma Membrane Transport Proteins; D050487:Glycine Plasma Membrane Transport Proteins; D026901:Membrane Transport Proteins; D050486:Serotonin Plasma Membrane Transport Proteins; D000254:Sodium-Potassium-Exchanging ATPase
keywords: Alzheimer's disease; amyloid β; astrocytes; neurodegeneration; transport