{"doi":"10.3389/fnagi.2021.754956","title":"Curcumin Reduced H2O2- and G2385R-LRRK2-Induced Neurodegeneration","abstract":"Mutations in leucine-rich repeat kinase 2 gene ( LRRK2 ) are the most frequent genetic factors contributing to Parkinson's disease (PD). G2385R- LRRK2 increases the risk for PD susceptibility in the Chinese population. However, the pathological role of G2385R- LRRK2 is not clear. In this study, we investigate the roles of G2385R-LRRK2 in neurodegeneration underlying PD pathogenesis using cell biology and pharmacology approaches. We demonstrated that expression of G2385R-LRRK2-induced neurotoxicity in human neuroblastoma SH-SY5Y and mouse primary neurons. G2385R-LRRK2 increased mitochondrial ROS, activates caspase-3/7, and increased PARP cleavage, resulting in neurotoxicity. Treatment with curcumin (an antioxidant) significantly protected against G2385R-LRRK2-induced neurodegeneration by reducing mitochondrial ROS, caspase-3/7 activation, and PARP cleavage. We also found that the cellular environmental stressor, H 2 O 2 significantly promotes both WT-LRRK2- and G2385R-LRRK2-induced neurotoxicity by increasing mitochondrial ROS, caspase-3/7 activation, and PARP cleavage, while curcumin attenuated this combined neurotoxicity. These findings not only provide a novel understanding of G2385R roles in neurodegeneration and environment interaction but also provide a pharmacological approach for intervention for G2385R-LRRK2-linked PD.","journal":"Frontiers in Aging Neuroscience","year":2021,"id":182324,"datarank":0.41588830833596724,"base_score":2.772588722239781,"endowment":2.772588722239781,"self_citation_contribution":0.41588830833596724,"citation_network_contribution":0.0,"self_endowment_contribution":0.41588830833596724,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":15,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9601,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":734183,"name":"Kai Li","orcid":"0000-0003-3140-9688","position":1,"is_corresponding":false},{"id":734184,"name":"Xiaobo Wang","orcid":"0009-0003-0759-0592","position":2,"is_corresponding":false},{"id":466918,"name":"Amber M. Smith","orcid":"0000-0002-7092-6904","position":3,"is_corresponding":false},{"id":232366,"name":"Bo Ning","orcid":"0000-0001-9437-7244","position":4,"is_corresponding":false},{"id":734185,"name":"Zhaohui Liu","orcid":"0000-0002-7482-7137","position":5,"is_corresponding":false},{"id":439710,"name":"Chun‐Feng Liu","orcid":"0000-0002-8364-0219","position":6,"is_corresponding":false},{"id":341295,"name":"Christopher A. Ross","orcid":"0000-0003-1882-5847","position":7,"is_corresponding":false},{"id":426507,"name":"Wanli W. Smith","orcid":"0000-0002-6482-5154","position":8,"is_corresponding":false},{"id":704513,"name":"Jinru Zhang","orcid":"0000-0001-5706-9031","position":0,"is_corresponding":true}],"reference_count":35,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:48:09.223560Z","pmid":"34720999","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}