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- Delivery Courier? Microglia Drop Neprilysin Off Near Plaques in Brain
Researchers genetically engineered human iPSC-microglia to deliver neprilysin when the cells are near amyloid plaques Both local injection and brain-wide engraftment of neprilysin-secreting microglia reduced Aβ pathology Only widespread engraftment helped reduce pathologies and improve neuronal density in the subiculum
- Microglia Build Plaques to Protect the Brain - ALZFORUM
Could it be that microglia build plaques rather than bust them? In the April 15 Nature Immunology, researchers led by Greg Lemke at the Salk Institute for Biological Studies, La Jolla, California, add to the evidence for this idea In a mouse model of amyloidosis, the researchers hobbled microglial
- Do Rod-Shaped Microglia Dampen Hyperexcitability in ALS?
Rod-shaped microglia appear in response to neuronal hyperactivity in TDP-43 mice The cells cozy up to dendrites and prune excitatory synapses Without rod-shaped microglia, hyperactivity worsens, and animals die sooner
- Harnessing human iPSC-microglia for CNS-wide delivery of disease . . .
Microglia Drop Neprilysin Off Near Plaques in Brain This proof-of-concept study brings forward several important findings Leveraging microglia—the brain’s primary immune cells, which are typically present at the scene of any pathology—as vehicles for therapeutic delivery introduces novelty into the field of microglial targeting
- Expunging Microglial Lipid Droplets Boosts Phagocytosis
Wu and colleagues confirmed that cultured-microglia-carrying lipid droplets struggled with phagocytosis, poorly engulfing fluorescently labeled inactivated E Coli or Aβ What if microglia were free of excessive lipids? To find out, researchers targeted FIT2, a protein embedded in the endoplasmic reticulum that helps lipid droplets form and bud
- Ferried Into Brain, TREM2 Antibody Stirs Microglia | ALZFORUM
It drove TREM2 signaling in cultured human microglia, inducing their proliferation and enhancing their phagocytosis In a mouse model of amyloidosis, the antibody slid into the brain, increased microglial activity, and boosted brain glucose metabolism
- Microglia protect against age-associated brain pathologies . . . - ALZFORUM
Both papers agree that the lack of microglia in adult mice results in neurodegeneration, brain calcifications, and myelin abnormalities, phenotypes resembling CSF1R-related leukoencephalopathy Transplantation of wild-type mouse human microglia rescued these phenotypes and protected against the development of the associated pathologies
- Part with PILRA, Power Up Microglia? - ALZFORUM
Unlike wild-type microglia, PILRA-less iMG barely changed gene expression in response to interferon-γ or lipopolysaccharide (LPS), suggesting they tone down their response to inflammatory stimuli In keeping with this, they released scant TNF-α, IL-6, IL-1β, and IP-10—all proinflammatory cytokines Their metabolome told a similar story
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