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Keywords {🔍}

cells, microglia, pubmed, article, google, scholar, cas, expression, ilβ, microglial, tspo, cell, levels, tgfβ, central, ctrl, analysis, human, mcm, activation, increased, inflammatory, neurosteroidogenesis, fig, observed, results, phenotype, medium, response, neurosteroids, hnpcs, protein, treatment, antiinflammatory, differentiation, data, activated, effects, time, signalling, activity, role, ligands, suggesting, translocator, proinflammatory, ligand, piga, estradiol, inhibition,

Topics {✒️}

amg/il-1β-treated c20 cells xbd-173/il-1β-treated c20 cells unique tgf-β–dependent molecular article download pdf dmem-f-12 serum-free medium real-time rt-pcr analysis il-1β-treated c20 cells c20 il-β-treated cells span intro/exon boundaries protease inhibitors—4 µg/ml apronitin amg/il-1β-treated sample amg/il-1β-treated cells endogenous ligand tgf-β il-1β cells pre-treated amg/il-1β microglia showed piga1138/il-1β c20 cells interleukin-1β-induced inflammatory signaling tert-butyl methyl ether reduces β-amyloid burden writing—original draft preparation full size image high-resolution mass spectrometer inflamed microglia pre-treated mcm piga1138/il-1β led tlr4/nf-kb pathway trem2-apoe pathway drives precast stain-free gels final rt-pcr reactions real time rt-pcr intracellular/extracellular aβ-fam ratio round coverslip pre-coated chemo-luminescent substrate ecl pi3k/nf-κb signaling transcription factor nf-κb nestin-expressing progenitor cells human granulosa-lutein cells lc/hr-ms investigations modulate nf-κb activation adult-derived human microglia beta-amyloid generation induced astrocyte-mediated neuroinflammatory responses hydroxylamine-derivatization hplc–ms pre-treatments slightly reduced central nervous system amg-treated c20 cells 5α/5β-reduced progesterone metabolites 3β-hydroxysteroid dehydrogenase activity embryonic-derived human microglia 5α/5β–reductase appeared c20 il-1β cells

Questions {❓}

• Gómez Morillas A, Besson VC, Lerouet D (2021) Microglia and neuroinflammation: what place for P2RY12?
• Ransohoff RM (2016) A polarizing question: do M1 and M2 microglia exist?
• Sneeboer MAM et al (2020) Microglial activation in schizophrenia: is translocator 18 kDa protein (TSPO) the right marker?

Schema {🗺️}

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         headline:18 kDa TSPO targeting drives polarized human microglia towards a protective and restorative neurosteroidome profile
         description:An aberrant pro-inflammatory microglia response has been associated with most neurodegenerative disorders. Identifying microglia druggable checkpoints to restore their physiological functions is an emerging challenge. Recent data have shown that microglia produce de novo neurosteroids, endogenous molecules exerting potent anti-inflammatory activity. Here, the role of neurosteroidogenesis in the modulation of microgliosis was explored in human microglia cells. In particular, CYP11A1 inhibition or TSPO pharmacological stimulation, crucial proteins involved in the rate limiting step of the neurosteroidogenic cascade, were employed. CYP11A1 inhibition led microglia to acquire a dysfunctional and hyperreactive phenotype, while selective TSPO ligands promoted the establishment of an anti-inflammatory one. Analysis of specific neurosteroid levels (neurosteroidome) identified allopregnanolone/pregnanolone as crucial metabolites allowing controlled activation of microglia. Importantly, the neurosteroid shift towards a greater androgenic/estrogenic profile supported the transition from pro-inflammatory to neuroprotective microglia, suggesting the therapeutic potential of de novo microglial neurosteroidogenesis stimulation for neuroinflammatory-related disorders.
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      headline:18 kDa TSPO targeting drives polarized human microglia towards a protective and restorative neurosteroidome profile
      description:An aberrant pro-inflammatory microglia response has been associated with most neurodegenerative disorders. Identifying microglia druggable checkpoints to restore their physiological functions is an emerging challenge. Recent data have shown that microglia produce de novo neurosteroids, endogenous molecules exerting potent anti-inflammatory activity. Here, the role of neurosteroidogenesis in the modulation of microgliosis was explored in human microglia cells. In particular, CYP11A1 inhibition or TSPO pharmacological stimulation, crucial proteins involved in the rate limiting step of the neurosteroidogenic cascade, were employed. CYP11A1 inhibition led microglia to acquire a dysfunctional and hyperreactive phenotype, while selective TSPO ligands promoted the establishment of an anti-inflammatory one. Analysis of specific neurosteroid levels (neurosteroidome) identified allopregnanolone/pregnanolone as crucial metabolites allowing controlled activation of microglia. Importantly, the neurosteroid shift towards a greater androgenic/estrogenic profile supported the transition from pro-inflammatory to neuroprotective microglia, suggesting the therapeutic potential of de novo microglial neurosteroidogenesis stimulation for neuroinflammatory-related disorders.
      datePublished:2025-01-06T00:00:00Z
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         Neuroinflammation
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         Cell Biology
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            name:Karolinska Institutet
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      affiliation:
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            address:
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            address:
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            address:
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               type:PostalAddress
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            address:
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            address:
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               type:PostalAddress
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            address:
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               type:PostalAddress
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      name:Department of Pharmacy, University of Pisa, Pisa, Italy
      name:Department of Pharmacy, University of Pisa, Pisa, Italy
      name:Center for Instrument Sharing, University of Pisa (CISUP), Pisa, Italy
      name:Department of Pharmacy, University of Pisa, Pisa, Italy
      name:Division of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden
      name:Department of Pharmacy, University of Pisa, Pisa, Italy
      name:Department of Pharmacy, University of Pisa, Pisa, Italy
      name:Department of Pharmacy, University of Pisa, Pisa, Italy
      name:Department of Pharmacy, University of Pisa, Pisa, Italy
      name:Center for Instrument Sharing, University of Pisa (CISUP), Pisa, Italy
      name:Department of Pharmacy, University of Pisa, Pisa, Italy
      name:Center for Instrument Sharing, University of Pisa (CISUP), Pisa, Italy
      name:Department of Pharmacy, University of Pisa, Pisa, Italy
      name:Center for Instrument Sharing, University of Pisa (CISUP), Pisa, Italy
      name:Department of Pharmacy, University of Pisa, Pisa, Italy
      name:Center for Instrument Sharing, University of Pisa (CISUP), Pisa, Italy
      name:Department of Pharmacy, University of Pisa, Pisa, Italy
      name:Center for Instrument Sharing, University of Pisa (CISUP), Pisa, Italy
      name:Department of Pharmacy, University of Pisa, Pisa, Italy
      name:Center for Instrument Sharing, University of Pisa (CISUP), Pisa, Italy
      name:Department of Pharmacy, University of Pisa, Pisa, Italy
      name:Center for Instrument Sharing, University of Pisa (CISUP), Pisa, Italy

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