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High throughput screening of patient's iPSC-derived neurons identifies gut microbial metabolites as a potential treatment for Alzheimer's disease.

ABSTRACT: High throughput screening of patient's iPSC-derived neurons identifies gut microbial metabolites as a potential treatment for Alzheimer's disease.

PROVIDER: PRJNA1254111 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR33247687_1.fastq.gz	Fastqsanger.gz
	SRR33247687_2.fastq.gz	Fastqsanger.gz
	SRR33247688_1.fastq.gz	Fastqsanger.gz
	SRR33247688_2.fastq.gz	Fastqsanger.gz
	SRR33247689_1.fastq.gz	Fastqsanger.gz

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High throughput screening of patient's iPSC-derived neurons identifies gut microbial metabolites as a potential treatment for Alzheimer's disease.

Project description:Altered gut microbial composition observed in Alzheimer’s disease patients drive microbial metabolome changes associated with AD pathogenesis; however, key microbial metabolites involved in this process and their functional roles are unknown. Here, we screened library of 352 gut metabolites in AD patient iPSC derived neurons for their ability to reduce phosphorylation of tau. We identified 4-methylcatechol, menaquinone-4 and agmatine as candidate metabolites associated with decreased tau phosphorylation and chose agmatine for further validatory studies. We demonstrated that Agmatine significantly reduce tau hyperphosphorylations (pTau181, pTau205 and pTau231) in AD patient iPSC-derived neurons and cerebral organoids. We also observed that agmatine treatment enhances learning and memory, reduces amyloid burden and neuroinflammation in a 5xFAD mouse model. Transcriptomics analysis from patient iPSC derived brain organoids suggested decreased expression of complement system pathway genes (e.g. C1S, C2, C3AR1, C5AR1) by agmatine treatment. The study also highlights agmatine as an important modulator of AD pathology via regulating C3aR-STAT3 axis and implicates it as a novel therapeutic target for AD.

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2022-01-27 | GSE95673 | GEO

Next Generation Sequencing of 12 human platelet's miRNA for Alzheimer's disease study

Project description:We obtained miRNA expression information from 12 human platelet samples using the NGS method. The patient group was divided into "Normal Young", "Normal Old" and "Alzheimer's disease". Twenty miRNAs whose expression gradually changed in 3 groups were selected. Among them, miR150-3p and miR150-5p were highly correlated with each other and had a high correlation with the patient's age. In addition, the expression of miR-150-3p and miR-150-5p showed a miRNA-imbalance phenomenon in which the ratio was specifically changed in Alzheimer's disease.

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Project description:High throughput screening of patient's iPSC-derived neurons identifies gut microbial metabolites as a potential treatment for Alzheimer's disease

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