The Ambiguous Role of Microglia in Aβ Toxicity: Chances for Therapeutic Intervention

Author(s): Sara Merlo, Simona Federica Spampinato, Grazia Ilaria Caruso, Maria Angela Sortino*

Journal Name: Current Neuropharmacology

Volume 18 , Issue 5 , 2020

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Graphical Abstract:


Abstract:

Amyloid-β (Aβ) has long been shown to be critical in Alzheimer’s disease pathophysiology. Microglia contributes to the earliest responses to Aβ buildup, by direct interaction through multiple receptors. Microglial cells operate Aβ clearance and trigger inflammatory/regenerative processes that take place in the long years of silent disease progression that precede symptomatic appearance. But in time and with aging, the fine balance between pro- and anti-inflammatory activity of microglia deranges, negatively impacting its Aβ-clearing ability. Furthermore, in recent years, microglial activation has proven to be much more complex than the mere dichotomic pro/antiinflammatory polarization previously accepted. Microglia can display a wide spectrum of phenotypes, which can even be mixed. On these bases, it is evident that while pharmacological intervention aiding microglia to prolong its ability to cope with Aβ buildup could be extremely relevant, its feasibility is hampered by such high complexity, which still needs to be completely understood.

Keywords: Alzheimer's disease, β-amyloid receptors, TREM2, CD33, neuroinflammation, microglial activation.

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