Elucidating the Interactive Roles of Glia in Alzheimer’s Disease Using Established and Newly Developed Experimental Models
- 1Brain Science Institute, Korea Institute of Science and Technology (KIST), South Korea
- 2Biological Sciences, University of North Carolina at Charlotte, United States
- 3Korea University of Science and Technology, South Korea
- 4Korea University of Science and Technology, South Korea
- 5Mechanical Engineering and Engineering Science, University of North Carolina at Charlotte, United States
- 6Biological Sciences, University of North Carolina at Charlotte, United States
- 7The Nanoscale Science Program, University of North Carolina at Charlotte, United States
- 8Center for Biomedical Engineering and Science, University of North Carolina at Charlotte, United States
Alzheimer’s disease (AD) is an irreversible neurodegenerative illness and the exact etiology of the disease remains unknown. It is characterized by long preclinical and prodromal phases with pathological features including an accumulation of amyloid-beta (Aβ) peptides into extracellular Aβ plaques in the brain parenchyma and the formation of intracellular neurofibrillary tangles (NFTs) within neurons as a result of abnormal phosphorylation of microtubule-associated tau proteins. In addition, prominent activation of innate immune cells is also observed and/or followed by marked neuroinflammation. While such neuroinflammatory responses may function in a neuroprotective manner by clearing neurotoxic factors, they can also be neurotoxic by contributing to neurodegeneration via elevated levels of proinflammatory mediators and oxidative stress, and altered levels of neurotransmitters, that underlie pathological symptoms including synaptic and cognitive impairment, neuronal death, reduced memory, and neocortex and hippocampus malfunctions. Glial cells, particularly activated microglia and reactive astrocytes appear to play critical and interactive roles in such dichotomous responses. Accumulating evidence clearly point to their critical involvement in the prevention, initiation, and progression, of neurodegenerative diseases, including AD. Here, we review recent findings on the roles of astrocyte-microglial interactions in neurodegeneration in the context of AD and discuss newly developed in vitro and in vivo experimental models that will enable more detailed analysis of glial interplay. An increased understanding of the roles of glia and the development of new exploratory tools are likely to be crucial for the development of new interventions for early stage AD prevention and cures.
Keywords: Neuroinflammation, Alzheimer's disease, Astrogliosis, Microgliosis, animal model, brain-on a chip, Astrogliosis-Microgliosis Axis (AMA)
Received: 26 Apr 2018;
Accepted: 04 Sep 2018.
Edited by:Alberto Serrano-Pozo, Massachusetts General Hospital, Harvard Medical School, United States
Reviewed by:Claire J. Garwood, University of Sheffield, United Kingdom
Yijuang Chern, National Research Program for Biopharmaceuticals, Taiwan
Copyright: © 2018 Chun, Marriott, Lee and Cho. 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: Prof. Hansnag Cho, University of North Carolina at Charlotte, Mechanical Engineering and Engineering Science, Charlotte, 28223, NC, United States, firstname.lastname@example.org