Mechanistic chain from microglial ISR activation to toxic lipid secretion and synapse loss

neurodegeneration open composite 69%
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Composite
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Description

PMID:39719704 discovered that microglial integrated stress response (ISR) activation induces dark microglia and toxic lipid secretion causing synapse loss in AD models. However, the specific lipid species mediating neurotoxicity, the full complement of ISR-driven secreted factors, and the precise mechanism of synapse impairment remain unresolved. The protective effect of ISR or lipid synthesis inhibition was shown, but the downstream neuronal pathways and whether this mechanism drives human AD progression is unknown.

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