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Microglial Piezo1 mechanosensitive channel as a therapeutic target in Alzheimer's disease

Erol D Ikiz1,2, Erin R Hascup2,3, Chilman Bae4

  • 1Department of Chemistry, School of Integrated Sciences, Sustainability, and Public Health, College of Health, Science, and Technology, University of Illinois at Springfield, Springfield, IL, United States.

Frontiers in Cellular Neuroscience
|July 3, 2024
PubMed

Insights

Microglia sense mechanical signals via Piezo1 channels, crucial for brain health and disease. Targeting these channels may offer new Alzheimer's disease therapies by enhancing amyloid-beta clearance.

Area of Science:

  • Neuroscience
  • Cell Biology
  • Immunology

Background:

  • Microglia, the CNS immune cells, regulate brain development, homeostasis, and neuroinflammation.
  • Their ability to sense and respond to mechanical cues in the central nervous system (CNS) is not fully understood.
  • Mechanical changes occur during development, aging, and in neurological diseases like Alzheimer's.

Purpose of the Study:

  • To review the role of microglial Piezo1 mechanosensitive channels in the CNS.
  • To explore Piezo1 as a potential therapeutic target for Alzheimer's disease (AD).
  • To discuss Piezo1's function in microglial clearance of amyloid-beta (Aβ).

Main Methods:

  • Literature review focusing on microglial mechanosensation and Piezo1 channels.
  • Analysis of existing studies on Piezo1 structure, function, and modulation.
  • Examination of Piezo1's role in microglial phagocytosis of Aβ.

Main Results:

  • Microglia possess Piezo1 channels that detect environmental mechanical stimuli.
  • Piezo1 activity influences microglial functions, including phagocytosis.
  • Dysfunctional Piezo1 may contribute to AD pathogenesis.

Conclusions:

  • Microglial Piezo1 channels are key mediators of mechanotransduction in the CNS.
  • Targeting microglial Piezo1 presents a promising therapeutic strategy for Alzheimer's disease.
  • Modulating Piezo1 could enhance the clearance of toxic amyloid-beta aggregates.
Keywords:
Mediterranean dietamyloid-beta plaques (Aβ plaque)durotaxisfatty acid (composition)immunomodulationmechanotransducer channelsneuroinflammationphagocytosis

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