{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["10(6)"],"submitter":["Santhosh Kumar S"],"pubmed_abstract":["Alpha-synuclein (αSyn) protein levels correlate with the risk and severity of Parkinson's disease and related neurodegenerative diseases. Lowering αSyn is being actively investigated as a therapeutic modality. Here, we systematically map the regulatory network that controls endogenous αSyn using sequential CRISPR-knockout and -interference screens in an αSyn gene (<i>SNCA</i>)-tagged cell line and induced pluripotent stem cell-derived neurons (iNeurons). We uncover αSyn modifiers at multiple regulatory layers, with amino-terminal acetyltransferase B (NatB) enzymes being the most potent endogenous αSyn modifiers in both cell lines. Amino-terminal acetylation protects the cytosolic αSyn from rapid degradation by the proteasome in a Ube2w-dependent manner. Moreover, we show that pharmacologic"],"journal":["Science advances"],"pagination":["eadj4767"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10857481"],"repository":["biostudies-literature"],"pubmed_title":["Sequential CRISPR screening reveals partial NatB inhibition as a strategy to mitigate alpha-synuclein levels in human neurons."],"pmcid":["PMC10857481"],"pubmed_authors":["Ndayisaba A","Khurana V","Roof J","Shalem O","Luk K","Buenaventura C","Naseri NN","Pather SR","Santhosh Kumar S","Spruce LA","Fazelinia H","Acosta K","Hallacli E","Rhoades E"],"additional_accession":[]},"is_claimable":false,"name":"Sequential CRISPR screening reveals partial NatB inhibition as a strategy to mitigate alpha-synuclein levels in human neurons.","description":"Alpha-synuclein (αSyn) protein levels correlate with the risk and severity of Parkinson's disease and related neurodegenerative diseases. Lowering αSyn is being actively investigated as a therapeutic modality. Here, we systematically map the regulatory network that controls endogenous αSyn using sequential CRISPR-knockout and -interference screens in an αSyn gene (<i>SNCA</i>)-tagged cell line and induced pluripotent stem cell-derived neurons (iNeurons). We uncover αSyn modifiers at multiple regulatory layers, with amino-terminal acetyltransferase B (NatB) enzymes being the most potent endogenous αSyn modifiers in both cell lines. Amino-terminal acetylation protects the cytosolic αSyn from rapid degradation by the proteasome in a Ube2w-dependent manner. Moreover, we show that pharmacologic","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Feb","modification":"2025-04-04T13:34:37.478Z","creation":"2025-04-04T13:34:37.478Z"},"accession":"S-EPMC10857481","cross_references":{"pubmed":["38335281"],"doi":["10.1126/sciadv.adj4767"]}}