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Updated: May 23, 2025
Isolation of Cortical Microglia with Preserved Immunophenotype and Functionality From Murine Neonates
Published on: January 30, 2014
Menopause triggers microglia-associated neuroinflammation in Parkinson's disease
Sehar Usman1, Amal Chandra Mondal1
1Cellular and Molecular Neurobiology Laboratory, School of Life Sciences, Jawaharlal Nehru University, New Delhi 110067, India.
Abstract:
Microglia, the immune cells of brain, can drive neurodegenerative diseases like Parkinson's disease (PD). The resting microglia can polarize into two extremes, either proinflammatory M1 or anti-inflammatory M2 phenotype under a specific microenvironment. Different transcriptional factors and the release of various cytokines characterize these states. The released proinflammatory markers from M1 microglia lead to neuroinflammation that ultimately causes irreversible loss of dopaminergic neurons in PD patients, on the contrary, the M2 microglia possess neuroprotective activity. PD is caused by aggregation and misfolding of α-synuclein in the affected dopaminergic neurons. The misfolded α-synuclein is cytotoxic and can propagate like a prion from one cell to the other, acting like a template, that can initiate the conversion of normal proteins into abnormal conformation. The extracellular α-synuclein can interact and polarize the microglia into the M1 phenotype resulting in inflammation, thereby driving the progression of PD. The progression of neuroinflammation-mediated neurodegeneration in PD is seen higher in menopausal women; likely due to the low circulating estrogen levels. Estrogen hormones possess neuroprotective activity, and one of the ways is that they can polarize the microglia into M2 phenotypes and reduce α-synuclein-mediated microglial activation. A detailed understanding of the signaling mechanisms underlying microglial polarization between M1 and M2 phenotypes is crucial for identifying druggable targets to reduce PD symptoms, including in menopausal women.
Insights
Microglia polarization influences Parkinson's disease (PD) progression. Targeting M1/M2 phenotypes, especially in menopausal women, may offer new therapeutic strategies for neuroinflammation and neuroprotection.
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- Microglia, the brain's immune cells, play a dual role in neurodegenerative diseases like Parkinson's disease (PD).
- Microglia exist in proinflammatory (M1) and anti-inflammatory (M2) states, influencing neuroinflammation and neuroprotection.
- Parkinson's disease involves α-synuclein aggregation, which can activate microglia and promote M1 polarization, exacerbating neuroinflammation.
Purpose of the Study:
- To explore the role of microglial polarization in Parkinson's disease pathogenesis.
- To investigate the impact of α-synuclein on microglial phenotype.
- To examine the potential neuroprotective effects of estrogen in modulating microglial responses in PD, particularly in menopausal women.
Main Methods:
- Analysis of microglial polarization markers (cytokines, transcriptional factors).
- Investigation of α-synuclein's interaction with microglia.
- Assessment of estrogen's effect on microglial phenotype and α-synuclein-mediated activation.
Main Results:
- M1 microglia contribute to neuroinflammation and dopaminergic neuron loss in PD.
- M2 microglia exhibit neuroprotective properties.
- Extracellular α-synuclein drives M1 polarization and neuroinflammation.
- Estrogen may promote M2 polarization and counteract α-synuclein-induced microglial activation, offering neuroprotection.
Conclusions:
- Microglial polarization is a critical factor in PD progression.
- Modulating microglial phenotype towards M2 offers a potential therapeutic avenue for PD.
- Estrogen's neuroprotective role, particularly in postmenopausal women, is linked to its influence on microglial polarization and α-synuclein pathology.
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