Mechanosensing and the Hippo Pathway in Microglia: A Potential Link to Alzheimer's Disease Pathogenesis?
Lucrezia Bruno1, Simge Karagil1, Almas Mahmood2
1Department of Biomolecular Sciences, Kingston University London, Kingston-upon-Thames KT1 2EE, UK.
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.
Insights
Microglia mechanosensing in Alzheimer's disease (AD) is explored. The Hippo pathway may be a key player in microglial responses and a therapeutic target for neurodegeneration.
Area of Science:
- Neuroscience
- Cell Biology
- Immunology
Background:
- Microglia, the immune cells of the central nervous system (CNS), are implicated in Alzheimer's disease (AD) pathogenesis.
- Understanding how microglia sense and respond to their environment is crucial for neurodegenerative disease research.
- Mechanosensing and mechanotransduction pathways in microglia are under active investigation.
Purpose of the Study:
- To review the potential role of the Hippo pathway in microglial mechanosensing.
- To explore the involvement of Hippo pathway components in Alzheimer's disease pathogenesis.
- To identify potential therapeutic targets for microglial-induced neurodegeneration in AD.
Main Methods:
- Literature review of existing research on microglia, mechanosensing, and the Hippo pathway.
- Analysis of evidence linking Hippo pathway components to microglial function in the context of AD.
- Synthesis of findings to propose the Hippo pathway as a target.
Main Results:
- Microglia exhibit mechanosensing capabilities, responding to their microenvironment's physical properties.
- The Hippo pathway is a known mechanosensing pathway involved in cellular processes.
- Evidence suggests potential involvement of Hippo pathway components in microglia relevant to AD.
Conclusions:
- The Hippo pathway warrants investigation as a critical mechanosensing pathway in microglia.
- Targeting the Hippo pathway could offer a novel therapeutic strategy for AD.
- Modulating microglial mechanotransduction via the Hippo pathway may prevent neurodegeneration.
