Microglial Store-operated Calcium Signaling in Health and in Alzheimer’s Disease

Author(s): James G. McLarnon*

Journal Name: Current Alzheimer Research

Volume 17 , Issue 12 , 2020


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Abstract:

The dysregulation of calcium signaling mechanisms in neurons has been considered a contributing factor to the pathogenesis evident in early-onset Alzheimer’s Disease (AD). However, considerably less is known concerning the possible impairment of Ca2+ mobilization in resident immune cell microglia. This review considers findings which suggest that a prominent pathway for non-excitable microglial cells, store-operated calcium entry (SOCE), is altered in the sporadic form of AD. The patterns of Ca2+ mobilization are first discussed with platelet-activating factor (PAF) stimulation of SOCE in adult, fetal and immortalized cell-line, human microglia in the healthy brain. In all cases, PAF was found to induce a rapid transient depletion of Ca2+ from endoplasmic reticulum (ER) stores, followed by a sustained entry of Ca2+ (SOCE). A considerably attenuated duration of SOCE is observed with ATP stimulation of human microglia, suggested as due to agonist actions on differential subtype purinergic receptors. Microglia obtained from AD brain tissue, or microglia treated with full-length amyloid-β peptide (Aβ42), show significant reductions in the amplitude of SOCE relative to controls. In addition, AD brain and Aβ42-treated microglia exhibit decreased levels of Ca2+ release from ER stores compared to controls. Changes in properties of SOCE in microglia could lead to altered immune cell response and neurovascular unit dysfunction in the inflamed AD brain.

Keywords: Human microglia, store-operated calcium entry (SOCE), platelet-activating factor (PAF), prolonged SOCE, amyloid- beta (Aβ), Alzheimer's disease (AD).

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Article Details

VOLUME: 17
ISSUE: 12
Year: 2020
Published on: 22 February, 2021
Page: [1057 - 1064]
Pages: 8
DOI: 10.2174/1567205018666210119143817
Price: $65

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