Microglial NF-κB drives tau spreading and toxicity in a mouse model of tauopathy
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA813402 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR18252100.fastq.gz | Fastqsanger.gz | |||
| SRR18252101.fastq.gz | Fastqsanger.gz | |||
| SRR18252102_1.fastq.gz | Fastqsanger.gz | |||
| SRR18252102_2.fastq.gz | Fastqsanger.gz | |||
| SRR18252103.fastq.gz | Fastqsanger.gz |
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Project description:Microglial NF-κB drives tau spreading and toxicity in a mouse model of tauopathy [snRNA-Seq]
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Project description:Microglial NF-κB drives tau spreading and toxicity in a mouse model of tauopathy [bulk RNA-Seq]
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Project description:Activation of microglia is a prominent pathological feature in tauopathies, including Alzheimer's disease. How microglia activation contributes to tau toxicity remains largely unknown. Here we show that nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling, activated by tau, drives microglial-mediated tau propagation and toxicity. Constitutive activation of microglial NF-κB exacerbated, while inactivation diminished, tau seeding and spreading in young PS19 mice. Inhibition of NF-κB activation enhanced the retention while reduced the release of internalized pathogenic tau fibrils from primary microglia and rescued microglial autophagy deficits. Inhibition of microglial NF-κB in aged PS19 mice rescued tau-mediated learning and memory deficits, restored overall transcriptomic changes while increasing neuronal tau inclusions. Single cell RNA-seq revealed that tau-associated disease states in microglia were diminished by NF-κB inactivation and further transformed by constitutive NF-κB activation. Our study establishes a role for microglial NF-κB signaling in mediating tau spreading and toxicity in tauopathy.
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