Elucidating the Interactive Roles of Glia in Alzheimer's Disease Using Established and Newly Developed Experimental Models

Frontiers in Neurology

C. Justin Lee¹  Heejung Chun³  Ian Marriott⁴  Hansang Cho⁶ 

[1] Bio-Med, University of Science and Technology, Daejeon, South Korea;Center for Biomedical Engineering and Science, University of North Carolina at Charlotte, Charlotte, NC, United States;Center for Glia-Neuron Interaction, Brain Science Institute, Korea Institute of Science and Technology, Seoul, South Korea;Department of Biological Sciences, University of North Carolina at Charlotte, Charlotte, NC, United States;Department of Mechanical Engineering and Engineering Science, University of North Carolina at Charlotte, Charlotte, NC, United States;The Nanoscale Science Program, University of North Carolina at Charlotte, Charlotte, NC, United States;

关键词: neuroinflammation;    Alzheimer's disease;    astrogliosis;    microgliosis;    animal models;    brain-on-a-chip;   

DOI  :  10.3389/fneur.2018.00797

来源: DOAJ

【 摘 要 】

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 evidences 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.

【 授权许可】

Unknown