Astrocytic transporters in Alzheimer's disease

TY - JOUR

T1 - Astrocytic transporters in Alzheimer's disease

AU - Ugbode, Christopher

AU - Hu, Yuhan

AU - Whalley, Benjamin J

AU - Peers, Chris

AU - Rattray, Marcus

AU - Dallas, Mark L

N1 - © 2017 The Author(s); published by Portland Press Limited on behalf of the Biochemical Society.

PY - 2017/2/1

Y1 - 2017/2/1

N2 - 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.

AB - 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.

KW - ATP-Binding Cassette Transporters

KW - Alzheimer Disease

KW - Animals

KW - Astrocytes

KW - GABA Plasma Membrane Transport Proteins

KW - Gene Expression Regulation

KW - Glucose Transport Proteins, Facilitative

KW - Glutamate Plasma Membrane Transport Proteins

KW - Glycine Plasma Membrane Transport Proteins

KW - Humans

KW - Membrane Transport Proteins

KW - Multigene Family

KW - Serotonin Plasma Membrane Transport Proteins

KW - Signal Transduction

KW - Sodium-Potassium-Exchanging ATPase

KW - Journal Article

KW - Review

KW - Research Support, Non-U.S. Gov't

U2 - 10.1042/BCJ20160505

DO - 10.1042/BCJ20160505

M3 - Review article

C2 - 28108584

SN - 0264-6021

VL - 474

SP - 333

EP - 355

JO - Biochemical journal

JF - Biochemical journal

IS - 3

ER -