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Molecular Mechanisms of Microglial Motility: Changes in Ageing and Alzheimer's Disease
Diana K Franco-Bocanegra1, Ciaran McAuley2, James A R Nicoll3,4
1Clinical Neurosciences, Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton SO16 6YD, UK. D.K.Franco-Bocanegra@soton.ac.uk.
Abstract:
Microglia are the tissue-resident immune cells of the central nervous system, where they constitute the first line of defense against any pathogens or injury. Microglia are highly motile cells and in order to carry out their function, they constantly undergo changes in their morphology to adapt to their environment. The microglial motility and morphological versatility are the result of a complex molecular machinery, mainly composed of mechanisms of organization of the actin cytoskeleton, coupled with a "sensory" system of membrane receptors that allow the cells to perceive changes in their microenvironment and modulate their responses. Evidence points to microglia as accountable for some of the changes observed in the brain during ageing, and microglia have a role in the development of neurodegenerative diseases, such as Alzheimer's disease. The present review describes in detail the main mechanisms driving microglial motility in physiological conditions, namely, the cytoskeletal actin dynamics, with emphasis in proteins highly expressed in microglia, and the role of chemotactic membrane proteins, such as the fractalkine and purinergic receptors. The review further delves into the changes occurring to the involved proteins and pathways specifically during ageing and in Alzheimer's disease, analyzing how these changes might participate in the development of this disease.
Insights
Microglia, the brain's immune cells, use actin cytoskeleton dynamics and membrane receptors for motility. Changes in these mechanisms contribute to brain aging and Alzheimer's disease progression.
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- Microglia are the primary immune cells in the central nervous system.
- They are crucial for defense against pathogens and injury.
- Microglial motility and morphology are key to their function.
Purpose of the Study:
- To detail the molecular mechanisms of microglial motility in healthy conditions.
- To explore the role of actin cytoskeleton dynamics and membrane receptors.
- To analyze changes in these mechanisms during aging and Alzheimer's disease.
Main Methods:
- Review of existing literature on microglial cell biology.
- Focus on actin cytoskeleton organization and associated proteins.
- Examination of chemotactic membrane proteins, including fractalkine and purinergic receptors.
Main Results:
- Microglial motility relies on actin dynamics and sensory membrane receptors.
- Specific proteins highly expressed in microglia are central to motility.
- Aging and Alzheimer's disease involve alterations in these proteins and pathways.
Conclusions:
- Microglial motility mechanisms are fundamental to brain health.
- Dysregulation of these mechanisms contributes to neurodegeneration.
- Understanding these changes is vital for developing therapies for aging and Alzheimer's disease.