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The Role of Glia in Alzheimer’s Disease

Review ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Neurosci. | doi: 10.3389/fnins.2018.00676

Microglia in Alzheimer's Disease: a role for Ion Channels

  • 1Reading School of Pharmacy, University of Reading, United Kingdom
  • 2Medical School, University of Exeter, United Kingdom
  • 3Bristol Medical School, University of Bristol, United Kingdom

Alzheimer’s disease is the most common form of dementia, it is estimated to affect over 40 million people worldwide. Classically, the disease has been characterised by the neuropathological hallmarks of aggregated extracellular amyloid-β and intracellular paired helical filaments of hyperphosphorylated tau. A wealth of evidence indicates a pivotal role for the innate immune system, such as microglia, and inflammation in the pathology of Alzheimer’s disease. The over production and aggregation of Alzheimer’s associated proteins results in chronic inflammation and disrupts microglial clearance of these depositions. Despite being non-excitable, microglia express a diverse array of ion channels which shape their physiological functions. In support of this, there is a growing body of evidence pointing to the involvement of microglial ion channels contributing to neurodegenerative diseases such as Alzheimer’s disease. In this review, we discuss the evidence for an array of microglia ion channels and their importance in modulating microglial homeostasis and how this process could be disrupted in Alzheimer’s disease. One promising avenue for assessing the role that microglia play in the initiation and progression of Alzheimer’s disease is through using induced pluripotent stem cell derived microglia. Here, we examine what is already understood in terms of the molecular underpinnings of inflammation in Alzheimer’s disease, and the utility that inducible pluripotent stem cell derived microglia may have to advance this knowledge. We outline the variability that occurs between the use of animal and human models with regards to the importance of microglial ion channels in generating a relevant functional model of brain inflammation. Overcoming these hurdles will be pivotal in order to develop new drug targets and progress our understanding of the pathological mechanisms involved in Alzheimer’s disease.

Keywords: Microglia, Alzheimer's disease (AD), Ion Channels, Stem Cells, iPS cells, TRPM Cation Channels

Received: 30 Mar 2018; Accepted: 07 Sep 2018.

Edited by:

Alberto Serrano-Pozo, Massachusetts General Hospital, Harvard Medical School, United States

Reviewed by:

Yueming LI, Memorial Sloan Kettering Cancer Center, United States
Hai M. Nguyen, University of California, Davis, United States  

Copyright: © 2018 Thei, Imm, Kaisis, Dallas and Kerrigan. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Talitha L. Kerrigan, University of Bristol, Bristol Medical School, Bristol, United Kingdom,