Abstract
Astrocytes play an important role in the central nervous system (CNS). Ion channels in these cells not only function in ion transport, and maintain water/ion metabolism homeostasis, but also participate in physiological processes of neurons and glial cells by regulating signaling pathways. Increasing evidence indicates the ion channel proteins of astrocytes, such as aquaporins (AQPs), transient receptor potential (TRP) channels, adenosine triphosphate (ATP)-sensitive potassium (K-ATP) channels, and P2X7 receptors (P2X7R), are strongly associated with oxidative stress, neuroinflammation and characteristic proteins in neurodegenerative disorders, including Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD) and amyotrophic lateral sclerosis (ALS). Since ion channel protein dysfunction is a significant pathological feature of astrocytes in neurodegenerative diseases, we discuss these critical proteins and their signaling pathways in order to understand the underlying molecular mechanisms, which may yield new therapeutic targets for neurodegenerative disorders.
Highlights
Astrocytes are the most abundant cells in the central nervous system (CNS)
AQP4-deficient mice were more likely to show neurotoxicity in response to MPTP with more reactive astrocytes and microglia in both the substantia nigra and ventral tegmental areas (Zhang et al, 2016). These results demonstrate the inhibitory effect of AQP4 channels in astrocytes on neuroinflammation in Parkinson’s disease (PD) models
Hu et al (2019) indicated that mitophagy was impaired in Kir6.1-deficient astrocytes of mice, which resulted in the accumulation of excess damaged mitochondria that could not be cleared by autophagy as evidenced by the downregulation of microtubule-associated protein light chain 3-II (LC3-II) and PTEN-induced putative kinase 1 (PINK1)/parkin, producing increased reactive oxygen species (ROS) and promoting neuroinflammation
Summary
Astrocytes are the most abundant cells in the central nervous system (CNS). These cells are capable of transporting ions, taking up neurotransmitters and producing neurotrophic factors to maintain the function and homeostasis of the CNS, where astrocytic ion channels have a pivotal role (Ikeshima-Kataoka, 2016; Verkhratsky and Nedergaard, 2018).
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