Neuroinflammation and Neurodegeneration Mechanisms

A CRISPRi/a platform in iPSC-derived microglia uncovers regulators of disease states

This study uses a CRISPRi/a platform in iPSC-derived microglia to identify genes regulating microglia states and their therapeutic targets.

Microglial and Astrocyte priming in the APP/PS1 model of Alzheimer’s Disease: increased vulnerability to acute inflammation and cognitive deficits

This study shows that in the APP/PS1 AD mouse model, microglia and astrocytes are primed to produce exaggerated inflammatory responses to secondary stimuli, leading to cognitive impairments.

Gene regulatory networks underlying human microglia maturation

This study defines age-specific brain environmental factors driving microglia phenotypes through transcriptomic and epigenomic analysis of human fetal and postnatal microglia.

Replicative senescence dictates the emergence of disease-associated microglia and contributes to Abeta pathology

This study shows that excessive microglial proliferation in Alzheimer's disease leads to replicative senescence and disease-associated microglia, contributing to Aβ pathology.

A map of transcriptional heterogeneity and regulatory variation in human microglia

The paper profiles gene expression in human microglia from 141 patients, identifies population shifts in acute brain injury, maps eQTLs, and fine-maps Alzheimer's risk variants using hIPSC-derived macrophages.

CDC50A dependent phosphatidylserine exposure induces inhibitory post-synapse elimination by microglia

The paper shows that CDC50A-dependent phosphatidylserine exposure acts as an 'eat-me' signal for microglia to eliminate inhibitory post-synapses.

Transcriptional landscape of human microglia reveals robust gene expression signatures that implicates age, sex and APOE-related immunometabolic pathway perturbations

The paper characterizes human microglia transcriptomes and identifies gene expression signatures linked to age, sex, and APOE-ε4, revealing immunometabolic pathway perturbations in neurodegeneration.

A role for the immune system-released activating agent (ISRAA) in the ontogenetic development of brain astrocytes

This study investigates the role of ISRAA in promoting the ontogeny of mouse brain astrocytes, showing its effects on proliferation, differentiation, and cytokine signaling.

The neuroinflammatory interleukin-12 signaling pathway drives Alzheimer's disease-like pathology by perturbing oligodendrocyte survival and neuronal homeostasis

This study identifies IL-12 as the main driver of neuroinflammation in Alzheimer's disease by affecting oligodendrocyte survival and neuronal homeostasis in a mouse model.

Microglial synaptic pruning on axon initial segment of dentate granule cells: sexually dimorphic effects on fear response of adult rats subjected to early life stress

This study shows that early life stress alters microglial synaptic pruning of axon initial segments in rats, with stronger effects in females, leading to increased fear responses in adulthood.

Ucp2-dependent microglia-neuronal coupling controls ventral hippocampal circuit function and anxiety-like behavior

The paper identifies Ucp2-dependent microglia-neuronal interactions that regulate ventral hippocampal circuit function and anxiety-like behavior through synapse remodeling and ROS dynamics.

The Alzheimer's disease risk factor APOE4 drives pro-inflammation in human astrocytes via HDAC-dependent repression of TAGLN3

This study shows APOE4 promotes inflammation in human astrocytes by repressing TAGLN3 through HDAC activity, linking it to Alzheimer's disease pathology.

Inflammatory cytokine profile and plasticity of brain and spinal microglia in response to ATP and glutamate

The paper compares the response of spinal cord and brain microglia to ATP and glutamate under physiologically relevant conditions and shows that these DAMPs do not significantly modulate cytokine release, but environmental factors can alter microglial inflammatory responses.

Systematically understanding the key roles of microglia in AD development

This study develops a 3D multi-scale model of AD to understand microglia's role in disease progression and predict therapeutic strategies.

The neuroprotective effect of meloxicam in a transient ischemia model involves an increase in axonal sprouting but a decrease in new neuron formation after 7 days ofreperfusion

This study examines the neuroprotective effects of meloxicam in a rat transient ischemia model, showing increased axonal sprouting but reduced new neuron formation after 7 days of reperfusion.

Meningeal inflammation in multiple sclerosis induces phenotypic changes in cortical microglia that differentially associate with neurodegeneration

The paper identifies two distinct microglial phenotypes in progressive MS patients and a rat model, showing they differentially associate with neurodegeneration.

Somatic junctions connect microglia and developing neurons

This study identifies somatic purinergic junctions between microglia and developing neurons across developmental stages, suggesting they facilitate communication and regulation of neurogenesis.

CSF1R inhibitor levels determine sex-specific phenotype of resilient microglia and neurofunctional rescue leading to extended survival in tauopathy mice

The paper evaluates CSF1R inhibitors in tauopathy mice, finding sex-specific functional outcomes and suggesting sex-dependent effects on neuroprotection.

Abi3 regulates microglial ramification and dynamic tissue surveillance in vivo.

This study shows Abi3 is essential for microglial morphology, distribution, and tissue surveillance in vivo, linking it to Alzheimer's disease risk.

Umbilical cord blood derived microglia-like cells to model COVID-19 exposure

This study generates patient-derived microglia-like cells from umbilical cord blood to model fetal brain immune responses to maternal SARS-CoV-2 exposure.

Microglial ERK signaling is a critical regulator of pro-inflammatory immune responses in Alzheimer’s disease

This study identifies ERK phosphorylation in microglia as a critical regulator of pro-inflammatory responses in Alzheimer’s disease using pre-clinical models and human proteomic data.

3D models of Alzheimer's disease patient microglia recapitulate disease phenotype and show differential drug responses compared to 2D

This study develops 3D models of Alzheimer's patient microglia that show distinct disease features and drug responses compared to 2D cultures.

Spleen glia are a transcriptionally unique glial subtype interposed between immune cells and sympathetic axons

The paper identifies spleen glia as a unique glial subtype that interacts with both sympathetic axons and immune cells through specific gene expression.

Microglial trogocytosis and the complement system regulate axonal pruning in vivo

The paper observes microglial trogocytosis of axons in vivo and identifies complement regulatory proteins that modulate this process and axonal pruning.

Microglia become hypofunctional and release metalloproteases and tau seeds after phagocytosing live neurons with P301S tau aggregates

The paper shows that microglia phagocytosing neurons with tau aggregates become hypofunctional and release tau seeds, contributing to tauopathy progression.

Multimodal single-cell/nucleus RNA-sequencing data analysis uncovers molecular networks between disease-associated microglia and astrocytes with implications for drug repurposing in Alzheimer's disease

INPP5D expression is associated with risk for Alzheimer's disease and induced by plaque-associated microglia

This study shows INPP5D expression increases in Alzheimer's disease, particularly in plaque-associated microglia, and suggests it may be a risk factor and therapeutic target.

Iron-loading is a prominent feature of activated microglia in Alzheimer's disease patients

The paper identifies iron-accumulating microglia in Alzheimer's brains, linking iron uptake to microglial activation and disease pathology.

Central inhibition of P2Y12R differentially regulates survival and neuronal loss in MPTP-induced Parkinsonism in mice

This study investigates the role of P2Y12R in Parkinson's disease progression in mice, showing that its inhibition can protect against neurodegeneration and neuroinflammation.

A Developmental Role for Microglial Presenilin 1 in Memory

This study shows that deleting Presenilin 1 in microglia during development enhances memory and neuronal activity in mice, with effects dependent on GluN2B and mitigating Alzheimer's symptoms.