Article

Identifying brain-penetrant small molecule modulators of human microglia using a cellular model of synaptic pruning

2024-12-23

Abstract excerpt

Microglia dysregulation is implicated across a range of neurodevelopmental and neurodegenerative disorders, making their modulation a promising therapeutic target. Using PBMC-derived induced microglia-like cells (piMGLCs) in a scalable assay, we screened 489 CNS-penetrant compounds for modulation of microglial phagocytosis of human synaptosomes in a validated assay for microglia-mediated synaptic pruning. Compound...

Topics

Open a Topic to create a Post that cites this publication.

Identifiers and source

Literature Corpus work: b4bf6495-711f-5ede-bf69-6ce48ce3c92c
DOI: 10.1101/2024.12.23.630139

Open publication

Related research

Semantic proximity does not establish scientific evidence.

Click a neighbor to travelStep 1 · 12 closest

Identifying brain-penetrant small molecule modulators of human microglia using a cellular model of synaptic pruningDOI 10.1101/2024.12.23.630139Read

A bottom-up approach identifies the antipsychotic and antineoplastic trifluoperazine and the ribose derivative deoxytubercidin as novel microglial phagocytosis inhibitorsSemantic proximity Read

An automated high-content synaptic phenotyping platform in human neurons and astrocytes reveals a role for BET proteins in synapse assemblySemantic proximity Read

Small Molecule Agonists of TREM2 Reprogram Microglia and Protect Synapses in Human Alzheimer’s ModelsSemantic proximity Read

Loss of function in the autism and schizophrenia-associated gene <i>CYFIP1</i> in human microglia supports a role in synaptic pruningSemantic proximity Read

Isolation of highly enriched primary human microglia for functional studies.Semantic proximity Read

Increased microglial synapse elimination in patient-specific models of schizophreniaSemantic proximity Read

Inflammation-enhanced synapse-specific phagocytosis by adult APP microglia in a microfluidic neuron–microglia co-culture modelSemantic proximity Read

Cytoplasmic-predominant Pten increases microglial activation and synaptic pruning in a murine model with autism-like phenotype.Semantic proximity Read

GW5074 Increases Microglial Phagocytic Activities: Potential Therapeutic Direction for Alzheimer’s DiseaseSemantic proximity Read

iPSC-derived microglia carrying the TREM2 R47H/+ mutation are proinflammatory and promote synapse loss.Semantic proximity Read

Controlling astrocyte-mediated synaptic pruning signals for schizophrenia drug repurposing with Deep Graph NetworksSemantic proximity Read

Human microglia in brain assembloids display region- specific diversity and respond to hyperexcitable neurons carrying <i>SCN2A</i> mutation: Microglial diversity and response in assembloidsSemantic proximity Read