Ugbode Chris, Hu Yuhan, Whalley Benjamin, Peers Chris, Rattray Marcus, Dallas Mark L
Department of Biology, University of York, Heslington, York YO10 5DD, U.K.
School of Pharmacy, University of Reading, Reading RG6 6UB, U.K.
Biochem J. 2017 Feb 1;474(3):333-355. doi: 10.1042/BCJ20160505.
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.
星形胶质细胞在维持中枢神经系统的健康和功能方面发挥着重要作用。越来越多的证据表明,在包括阿尔茨海默病(AD)在内的神经疾病早期,星形胶质细胞会发生细胞和分子变化。这些变化可能反映了从神经保护表型到神经毒性表型的转变。鉴于目前缺乏针对AD的疾病修饰疗法,星形胶质细胞已成为一个有趣且可行的治疗干预靶点。星形胶质细胞转运系统涵盖了一系列参与代谢支持、神经传递和突触结构的蛋白质。因此,针对单个转运蛋白家族进行特异性靶向有可能抑制神经退行性变,这是AD的一个典型特征。在400个转运蛋白超家族中,只有少数在星形胶质细胞中表达,有证据表明其中一部分与AD有关。在此,我们综述了动物和人类研究中报道的六个与AD相关的星形胶质细胞转运蛋白亚家族的现有证据。本综述证实星形胶质细胞确实是一个可行的靶点,强调了研究星形胶质细胞的复杂性,并为挖掘星形胶质细胞在攻克AD方面的潜力提供了未来的指导方向。