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Updated: Dec 18, 2025
Isolation of Cortical Microglia with Preserved Immunophenotype and Functionality From Murine Neonates
Published on: January 30, 2014
Cathepsin regulation on microglial function
1Department of Pharmacology, Faculty of Pharmacy, Yasuda Women's University, Hiroshima 731-0153, Japan.
Abstract:
Microglia, the resident mononuclear phagocyte population in the brain, have long been implicated in the pathology of neurodegenerative age-associated disorders. However, activated microglia have now been identified as homeostatic keepers in the brain, because they are involved in the initiation and resolution of neuropathology. The complex roles of activated microglia appear to be linked to change from inflammatory and neurotoxic to anti-inflammatory and neuroprotective phenotypes. Increased expression and secretion of various cathepsins support roles of activated microglia in chronic neuroinflammation, the neurotoxic M1-like polarization and neuronal death. Moreover, changes in expression and localization of microglial cathepsin B play a critical role in the acceleration of the brain aging. Beyond the role as brain-resident macrophages, many lines of evidence have shown that microglia have essential roles in the maturation and maintenance of neuronal circuits in the developing and adult brain. Cathepsin S secreted from microglia induces the diurnal variation of spine density of cortical neurons though proteolytic modification of peri-synaptic extracellular matrix molecules. In this review, I highlight the emerging roles of cathepsins that support the roles of microglia in both normal healthy and pathological brains. In addition, I discuss cathepsin inhibitors as potential therapeutic targets for brain disorders.
Insights
Activated microglia, crucial for brain health, shift between inflammatory and protective roles. Cathepsins, enzymes secreted by microglia, are key to neuroinflammation, brain aging, and neuronal circuit maintenance, offering therapeutic targets.
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- Microglia, the brain's immune cells, are increasingly recognized for their dual roles in both neurodegeneration and maintaining brain homeostasis.
- Activated microglia can adopt different phenotypes, influencing inflammatory and protective responses in the central nervous system.
Purpose of the Study:
- To review the multifaceted roles of cathepsins, enzymes produced by microglia, in brain health and disease.
- To explore how cathepsins contribute to microglial functions in both physiological and pathological conditions.
- To discuss the potential of targeting cathepsins for therapeutic interventions in neurological disorders.
Main Methods:
- Literature review focusing on microglial function, cathepsin expression, and neuroinflammation.
- Analysis of studies investigating the impact of cathepsins on microglial polarization and neuronal health.
- Synthesis of evidence linking microglial cathepsins to brain aging and synaptic plasticity.
Main Results:
- Increased cathepsin expression in activated microglia correlates with chronic neuroinflammation, M1-like polarization, and neuronal death.
- Cathepsin B dysregulation contributes to accelerated brain aging.
- Microglial cathepsin S influences synaptic plasticity and neuronal circuit maintenance.
Conclusions:
- Cathepsins play critical, diverse roles in microglia-mediated processes within both healthy and diseased brains.
- Modulating cathepsin activity presents a promising therapeutic strategy for various brain disorders.
- Understanding cathepsin functions is essential for developing targeted treatments for neurodegenerative diseases and aging.
