{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE307nnn/GSE307275/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Transcriptomics"],"species":["Mus musculus"],"gds_type":["Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE307275"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Effect of mutation of LRRK2-P1446L on gene expression in substantia nigra of 16 months C57BL/6 mice","description":"Parkinson's disease (PD) is characterized by the progressive loss of dopaminergic neurons, with growing evidence implicating leucine-rich repeat kinase 2 (LRRK2) and neuroinflammation in its pathogenesis. In this study, we investigated the novel LRRK2 P1446L mutation and demonstrated its pivotal role in driving dopaminergic neurodegeneration through the dysregulation of death-associated protein kinase 1 (DAPK1)-mediated neuronal survival pathways. We found that this mutation induces DAPK1 overexpression, which concurrently activates mitochondrial apoptosis and exacerbates neuroinflammation via PI3K-Akt-dependent NF-κB activation. Notably, we identified a previously unrecognized DAPK1-Tuftsin regulatory axis, wherein DAPK1 upregulation suppresses the neuroprotective peptide Tuftsin, thereby aggravating neuronal vulnerability. Our findings establish DAPK1 as a central node linking LRRK2 P1446L to multiple PD-related pathological processes, and propose combined targeting of DAPK1 activity and Tuftsin restoration as a promising therapeutic strategy for LRRK2-associated Parkinson's disease.","dates":{"publication":"2026/09/01"},"accession":"GSE307275","cross_references":{"GSM":["GSM9220309","GSM9220313","GSM9220312","GSM9220314","GSM9220311","GSM9220310"],"GPL":["24247"],"GSE":["307275"],"taxon":["Mus musculus"]}}