{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["16(1)"],"submitter":["Yin S"],"pubmed_abstract":["Parkinson's disease (PD) involves both mitochondrial dysfunction and Lewy body pathology. However molecular links between these features remain unclear. Here, we identify Presenilin-associated rhomboid-like protein (PARL) as a Lewy body component, RARL regulates mitochondrial apoptosis via interacting with orphan nuclear receptor Nur77. Clinical profiling revealed reduced plasma PARL levels in 71 PD patients versus controls (p < 0.001), which correlated with disease severity. In MPP<sup>+</sup>/MPTP models, PARL depletion amplified BAX activation and caspase-3 cleavage, driving neuronal death. Mechanistically, mitochondrial translocation of Nur77 stabilized PARL-BCL-2 complexes, suppressing apoptosis. AlphaFold2-guided structural modeling uncovered a PARL α-helix essential for Nur77 bindin"],"journal":["Cell death & disease"],"pagination":["700"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12501375"],"repository":["biostudies-literature"],"pubmed_title":["PARL stabilizes mitochondrial BCL-2 via Nur77-mediated scaffolding as a therapeutic strategy for Parkinson's disease."],"pmcid":["PMC12501375"],"pubmed_authors":["Shen M","Lai X","Wu J","Jin W","Yu M","Yan J","Zhai Y","Yin S","Song R","Zhang Y","Ma H","Xu Y"],"additional_accession":[]},"is_claimable":false,"name":"PARL stabilizes mitochondrial BCL-2 via Nur77-mediated scaffolding as a therapeutic strategy for Parkinson's disease.","description":"Parkinson's disease (PD) involves both mitochondrial dysfunction and Lewy body pathology. However molecular links between these features remain unclear. Here, we identify Presenilin-associated rhomboid-like protein (PARL) as a Lewy body component, RARL regulates mitochondrial apoptosis via interacting with orphan nuclear receptor Nur77. Clinical profiling revealed reduced plasma PARL levels in 71 PD patients versus controls (p < 0.001), which correlated with disease severity. In MPP<sup>+</sup>/MPTP models, PARL depletion amplified BAX activation and caspase-3 cleavage, driving neuronal death. Mechanistically, mitochondrial translocation of Nur77 stabilized PARL-BCL-2 complexes, suppressing apoptosis. AlphaFold2-guided structural modeling uncovered a PARL α-helix essential for Nur77 bindin","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Oct","modification":"2026-06-04T05:58:37.745Z","creation":"2026-05-06T03:07:48.579Z"},"accession":"S-EPMC12501375","cross_references":{"pubmed":["41052999"],"doi":["10.1038/s41419-025-08035-8"]}}