Publications by authors named "M Khakpour"

The brain's primary immune cells, microglia, are a leading causal cell type in Alzheimer's disease (AD). Yet, the mechanisms by which microglia can drive neurodegeneration remain unresolved. Here, we discover that a conserved stress signaling pathway, the integrated stress response (ISR), characterizes a microglia subset with neurodegenerative outcomes.

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How microglia digest Alzheimer's fibrillar amyloid-beta (Aβ) plaques that are too large to be phagocytosed is not well understood. Here, we show that primary microglial cells create acidic extracellular compartments, lysosomal synapses, on model plaques and digest them with exocytosed lysosomal enzymes. This mechanism, called digestive exophagy, is confirmed by electron microscopy in 5xFAD mouse brains, which shows that a lysosomal enzyme, acid phosphatase, is secreted toward the plaques in structures resembling lysosomal synapses.

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The hippocampus is a heterogenous structure that exhibits functional segregation along its longitudinal axis. We recently showed that in male mice, microglia, the brain's resident immune cells, differ between the dorsal (DH) and ventral (VH) hippocampus, impacting long-term potentiation (LTP) mainly through the CX3CL1-CX3CR1 signaling. Here, we assessed the specific features of the hippocampal poles in female mice, demonstrating a similar LTP amplitude in VH and DH in both control and Cx3cr1 knock-out mice.

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Article Synopsis
  • * The researchers found that dark microglia interact with blood vessels and synapses and engage in trogocytosis, meaning they take pieces of pre-synaptic axon terminals.
  • * They discovered that dark microglia express specific proteins like CLEC7a, LPL, and TREM2, and that TREM2 is crucial for their function, indicating their important role in synaptic pruning and brain development.
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Air pollution poses a critical global challenge with severe environmental and human health implications. The associated health risks, including premature mortality, underscore the urgency of effective mitigation strategies. Many studies focus on control strategies without considering specific contaminant types, and there is a notable gap in research on cost-effective, eco-friendly methods, especially in countries facing substantial air pollution challenges.

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