ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2025
Role of Testosterone Signaling in Microglia: A Potential Role for Sex-Related Differences in Alzheimer's Disease.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
What it found
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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.
The trial behind it
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Who cites it
6 citing papers in PubMed.
- Expression of GPR34 in microglia remains stable in human Alzheimer's disease.Acta neuropathologica · 2026Article
- Sex Differences in Metabolite-Immune Circuits of Neuroinflammation.Immunological reviews · 2026Review
- Sex hormone dysregulation after traumatic brain injury: interactions with sleep disturbances and seizure susceptibility.Frontiers in neuroscience · 2026Review
- Dynamic Alterations in Testicular Autophagy in Prepubertal Mice.Journal of developmental biology · 2025Article
- Role of Testosterone Signaling in Microglia: A Potential Role for Sex-Related Differences in Alzheimer's Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Longitudinal trajectories of cognitive decline and temporal lobe atrophy based on baseline gonadotropins and testosterone.Frontiers in neuroscience · 2025Article
Corrections and comments
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Authors and funding
9 authors.
Funding
Abstract
Alzheimer's disease (AD) is less prevalent in men than in women, although mechanisms remain unclear. Microglia degrade aggregated amyloid β (Aβ) through the lysosomal system, including autophagy. G protein-coupled receptor family C group 6 member A (GPRC6A), predominantly expressed in mouse microglial MG6 cells, is a primary mediator of testosterone signaling. This study examines testosterone's role in modulating Aβ-induced autophagy in microglia. Testosterone promotes Aβ-induced autophagy leading to Aβ clearance in MG6 cells by suppressing extracellular signal-regulated kinase (ERK) phosphorylation and subsequently inhibiting mammalian target of rapamycin (mTOR) activation, which is abrogated by shRNA knockdown of GPRC6A. In in vivo experiments with male 5xFAD AD model mice, Aβ clearance activity is associated with autophagy in microglia and is reduced by orchiectomy, but restored by testosterone supplementation. ERK phosphorylation in the brains of male AD model mice is upregulated by orchiectomy. Therefore, testosterone is involved in autophagy-mediated Aβ clearance in microglia. Aβ accumulation in human brain samples from patients with AD is significantly lower in men than in women, with less pronounced colocalization of Aβ with p62 aggregates, suggesting enhanced autophagic activity in men. In conclusion, testosterone enhances Aβ-induced autophagy in microglia, possibly contributing to lower susceptibility to AD in men.
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Registered trials
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.