Mechanosensing and the Hippo Pathway in Microglia: A Potential Link to Alzheimer’s Disease Pathogenesis?

Abstract

The activation of microglia, the inflammatory cells of the central nervous system (CNS), has been linked to the pathogenesis of Alzheimer’s disease and other neurodegenerative diseases. How microglia sense the changing brain environment, in order to respond appropriately, is still being elucidated. Microglia are able to sense and respond to the mechanical properties of their microenvironment, and the physical and molecular pathways underlying this mechanosensing/mechanotransduction in microglia have recently been investigated. The Hippo pathway functions through mechanosensing and subsequent protein kinase cascades, and is critical for neuronal development and many other cellular processes. In this review, we examine evidence for the potential involvement of Hippo pathway components specifically in microglia in the pathogenesis of Alzheimer’s disease. We suggest that the Hippo pathway is worth investigating as a mechanosensing pathway in microglia, and could be one potential therapeutic target pathway for preventing microglial-induced neurodegeneration in AD.

Helicobacter pylori Urease: Potential Contributions to Alzheimer’s Disease

“…Microglia are the main cells of the brain’s innate immune system, displaying macrophage-like characteristics. Microglial activation into an M1 phenotype leads to an increase in pro-inflammatory cytokines, which contributes to neurotoxicity [ 39 ]. Our data showed that HPU-activated BV-2 cells produced ROS at the highest tested dose, and showed a marked reduction in viability after 24 h of treatment ( Figure 2 ).…”

Emerging roles of the Hippo signaling pathway in modulating immune response and inflammation‐driven tissue repair and remodeling

“…Microglial activation has been associated with a destructive cellular response that drives neuronal cell death in ischemic stroke [126,127]. Zhao S et al [22] demonstrated that MST1 activates stroke-induced microglial activation as marked by CD11b in ischemic striatum of mice challenged to transient middle cerebral artery occlusion (tMCAO).…”

Piezo1 channel‐mediated Ca2+ signaling inhibits lipopolysaccharide‐induced activation of the NF‐κB inflammatory signaling pathway and generation of TNF‐α and IL‐6 in microglial cells

“…This finding is intriguing, as it strikingly contrasts with other recent studies reporting that Piezo1 channel activation in macrophages, myeloid cells, and nucleus pulposus cells promotes pro‐inflammatory responses (Atcha et al, 2021; Solis et al, 2019; Sun et al, 2022). Microglial cells are highly mobile both under physiological and pathological conditions, and able to sense mechanical signals in their microenvironments (Ayata & Schaefer, 2020; Bruno et al, 2021; Davalos et al, 2005). A recent study shows expression of the Piezo1 channel in BV2 microglial cells (Liu et al, 2021).…”