Evidence map›Paper›PMID 36766684›Full record

ArticleCells2023

Sex-Specific Microglial Responses to Glucocerebrosidase Inhibition: Relevance to GBA1-Linked Parkinson's Disease.

Electra Brunialti, Alessandro Villa, Marco Toffoli, Sara Lucas Del Pozo, Nicoletta Rizzi, Clara Meda, Adriana Maggi, Anthony H V Schapira, Paolo Ciana

Open access · goldAbstract read
In one paragraph

Article in Cells, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
3.7field-weighted citation impact, top 6% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

6 citing papers in PubMed, 21 citations in OpenAlex.

  1. Article
  2. Review
  3. Review
  4. Gut-Brain Axis: Focus on Sex Differences in Neuroinflammation.International journal of molecular sciences · 2024
    Review
  5. Article
  6. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 2 institutions in 3 countries.

Electra BrunialtiDepartment of Health Sciences, University of Milan, 20146 Milan, Italy.ORCID 0000-0002-0247-3819
Alessandro VillaDepartment of Health Sciences, University of Milan, 20146 Milan, Italy.ORCID 0000-0002-7445-916X
Marco ToffoliDepartment of Clinical and Movement Neurosciences, Queen Square Institute of Neurology, University College London, Royal Free Campus, London NW3 2PF, UK.ORCID 0000-0002-3255-9648
Sara Lucas Del PozoDepartment of Clinical and Movement Neurosciences, Queen Square Institute of Neurology, University College London, Royal Free Campus, London NW3 2PF, UK.
Nicoletta RizziAnimal Care Unit, University of Milan, 20146 Milan, Italy.
Clara MedaDepartment of Health Sciences, University of Milan, 20146 Milan, Italy.
Adriana MaggiDepartment of Pharmaceutical Sciences, University of Milan, 20146 Milan, Italy.ORCID 0000-0001-5700-5273
Anthony H V SchapiraDepartment of Clinical and Movement Neurosciences, Queen Square Institute of Neurology, University College London, Royal Free Campus, London NW3 2PF, UK.
Paolo CianaDepartment of Health Sciences, University of Milan, 20146 Milan, Italy.
University of Milan · ITThe Royal Free Hospital · GB

Funding

Medical Research Council MR/T046007/1
6 · The paper itself

Abstract

Microglia are heterogenous cells characterized by distinct populations each contributing to specific biological processes in the nervous system, including neuroprotection. To elucidate the impact of sex-specific microglia heterogenicity to the susceptibility of neuronal stress, we video-recorded with time-lapse microscopy the changes in shape and motility occurring in primary cells derived from mice of both sexes in response to pro-inflammatory or neurotoxic stimulations. With this morpho-functional analysis, we documented distinct microglia subpopulations eliciting sex-specific responses to stimulation: male microglia tended to have a more pro-inflammatory phenotype, while female microglia showed increased sensitivity to conduritol-B-epoxide (CBE), a small molecule inhibitor of glucocerebrosidase, the enzyme encoded by the GBA1 gene, mutations of which are the major risk factor for Parkinson's Disease (PD). Interestingly, glucocerebrosidase inhibition particularly impaired the ability of female microglia to enhance the Nrf2-dependent detoxification pathway in neurons, attenuating the sex differences observed in this neuroprotective function. This finding is consistent with the clinical impact of GBA1 mutations, in which the 1.5-2-fold reduced risk of developing idiopathic PD observed in female individuals is lost in the GBA1 carrier population, thus suggesting a sex-specific role for microglia in the etiopathogenesis of PD-GBA1.

Indexed as

Parkinson DiseaseAnimalsFemaleGlucosylceramidaseMaleMiceMicrogliaNeuronsGBA protein, humanGlucosylceramidaseglucocerebrosidase (GCase)microgliaParkinson’s Disease (PD)sex-differenceshape descriptors

Identifiers

PMID36766684
PMCPMC9913749
OpenAlexW4316690364

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.