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.
Highlights
The role of inflammation in the pathogenesis of chronic diseases, including neurodegenerative disease, is an area of intense current research
We examine evidence of a potential mechanotransductory role of the Hippo pathway in microglia and consider what is known about the role of this pathway in microglia in the pathogenesis of Alzheimer’s disease (AD)
These findings suggest that aberrant downregulation of Yes-associated protein (YAP) may have a role in early AD pathogenesis; it can be hypothesised that this could be perhaps by reducing healthy clearance of Aβ or tau by microglia, and/or by permitting proinflammatory microglial activation
Summary
The role of inflammation in the pathogenesis of chronic diseases, including neurodegenerative disease, is an area of intense current research. AD is characterised by the presence of extracellular amyloid-beta (Aβ) protein aggregates, named plaques, as well as intracellular neurofibrillary tangles (NFTs) of hyperphosphorylated tau protein, in central nervous system (CNS) tissue, and widespread CNS neuronal cell death and brain tissue atrophy [4,5]. Both genetic and environmental factors are thought to contribute to AD development. Many recent findings have implicated microglia, the immune cells of the mammalian central nervous system (CNS), in the initiation and pathogenesis of Alzheimer’s disease and other neurological diseases featuring neuroinflammation, but the molecular mechanisms underlying this are not yet well understood.
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