Alzheimer's disease: microglia targets and their modulation to promote amyloid phagocytosis and mitigate neuroinflammation.

Expert Opinion on Therapeutic Targets
Shehata Anwar, S Rivest

Abstract

Introduction: Despite the revolutionary progress in neurodegenerative disease research, there is no cure for Alzheimer's disease (AD). This is a chronic progressive neurodegenerative disease affecting aged people and is associated with chronic neuroinflammation and amyloid-beta (Aβ) deposition in the brain parenchyma. Microglia, the resident myeloid cells in the central nervous system, are critically involved in the pathogenesis of AD and have emerged as a potential therapeutic target for treating or preventing AD. The failure of microglia to keep up with persistent amyloid-beta development along with secretion of inflammatory cytokines is detrimental to neurons and favors Aβ accumulation.Areas covered: This review illuminates the latest research that is focused on molecules and their intracellular targets that promote microglial phagocytosis and /or its polarization to an anti-inflammatory state.Expert opinion: A robust inflammatory response of microglia is not necessary to improve their efficiency of Aβ clearance. The challenge is to master inflammatory/anti-inflammatory phenotypes depending on the stage of AD and to maintain efficient responses to remove Aβ. Therefore, promoting microglia phagocytosis without a persistent ex...Continue Reading

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Citations

Dec 15, 2020·Journal of Neurochemistry·Nofar Stolero, Dan Frenkel
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