{"doi":"10.1016/j.neuint.2015.08.006","title":"Antioxidant peroxiredoxin 6 protein rescues toxicity due to oxidative stress and cellular hypoxia in vitro, and attenuates prion-related pathology in vivo","abstract":null,"journal":"Neurochemistry International","year":2015,"id":676893,"datarank":0.5244761342199721,"base_score":3.4965075614664802,"endowment":3.4965075614664802,"self_citation_contribution":0.5244761342199721,"citation_network_contribution":0.0,"self_endowment_contribution":0.5244761342199721,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":32,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1768582,"name":"Maitea Guridi","orcid":null,"position":1,"is_corresponding":false},{"id":302093,"name":"Sandrine Sanchez","orcid":"0000-0003-3050-5862","position":2,"is_corresponding":false},{"id":1768583,"name":"Martin J. Sadowski","orcid":null,"position":3,"is_corresponding":false},{"id":959446,"name":"Ayodeji A. Asuni","orcid":"0000-0003-3488-6893","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Antioxidant peroxiredoxin 6 protein rescues toxicity due to oxidative stress and cellular hypoxia in vitro, and attenuates prion-related pathology in vivo","abstract":"Protein misfolding, mitochondrial dysfunction and oxidative stress are common pathomechanisms that underlie neurodegenerative diseases. In prion disease, central to these processes is the post-translational transformation of cellular prion protein (PrP(c)) to the aberrant conformationally altered isoform; PrP(Sc). This can trigger oxidative reactions and impair mitochondrial function by increasing levels of peroxynitrite, causing damage through formation of hydroxyl radicals or via nitration of tyrosine residues on proteins. The 6 member Peroxiredoxin (Prdx) family of redox proteins are thought to be critical protectors against oxidative stress via reduction of H2O2, hydroperoxides and peroxynitrite. In our in vitro studies cellular metabolism of SK-N-SH human neuroblastoma cells was significantly decreased in the presence of H2O2 (oxidative stressor) or CoCl2 (cellular hypoxia), but was rescued by treatment with exogenous Prdx6, suggesting that its protective action is in part mediated through a direct action. We also show that CoCl2-induced apoptosis was significantly decreased by treatment with exogenous Prdx6. We proposed a redox regulator role for Prdx6 in regulating and maintaining cellular homeostasis via its ability to control ROS levels that could otherwise accelerate the emergence of prion-related neuropathology. To confirm this, we established prion disease in mice with and without astrocyte-specific antioxidant protein Prdx6, and demonstrated that expression of Prdx6 protein in Prdx6 Tg ME7-animals reduced severity of the behavioural deficit, decreased neuropathology and increased survival time compared to Prdx6 KO ME7-animals. We conclude that antioxidant Prdx6 attenuates prion-related neuropathology, and propose that augmentation of endogenous Prdx6 protein represents an attractive adjunct therapeutic approach for neurodegenerative diseases.","is_dataset_classified":null,"base_score":3.4965075614664802,"endowment":3.4965075614664802,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"26265052","pmcid":"PMC4641785","openalex_id":"https://openalex.org/W1844785966","authors":[],"funders":[{"funder_name":"Alzheimer's Association","grant_id":"NIRG-10-173233","title":null},{"funder_name":"NIH","grant_id":"R01 AG029635","title":null},{"funder_name":"NIH","grant_id":"K02 AG034176","title":null},{"funder_name":"NIA NIH HHS","grant_id":"P30 AG008051","title":null},{"funder_name":"National Institutes of Health","grant_id":"1R01AG029635-01A2","title":"Therapeutic Monoclonal Antibodies for Human Prion Diseases"},{"funder_name":"National Institutes of Health","grant_id":"5K02AG034176-05","title":"Peptoid Antagonists of the ApoE/ABeta Interaction as a Novel Anti-ABeta Therapy"}],"total_grants":6,"fwci":0.6888,"citation_percentile":0.68612413,"influential_citations":0,"citation_trend":[{"year":2016,"count":1},{"year":2017,"count":1},{"year":2018,"count":3},{"year":2019,"count":2},{"year":2020,"count":3},{"year":2021,"count":6},{"year":2022,"count":2},{"year":2023,"count":4},{"year":2024,"count":3},{"year":2025,"count":5},{"year":2026,"count":2}],"oa_status":"green","license":"Elsevier TDM","oa_locations":[{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/4641785","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/4641785","host_type":"repository"},{"url":"https://api.elsevier.com/content/article/PII:S0197018615300346?httpAccept=text/xml","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S0197018615300346?httpAccept=text/plain","host_type":"publisher"},{"url":"https://doi.org/10.1016/j.neuint.2015.08.006","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/26265052","host_type":"repository"},{"url":"http://doi.org/10.1016/j.neuint.2015.08.006>).","host_type":"repository"},{"url":"https://europepmc.org/articles/pmc4641785?pdf=render","host_type":""},{"url":"https://dx.doi.org/10.1016/j.neuint.2015.08.006","host_type":""},{"url":"https://eprints.soton.ac.uk/383006/1/Asuni_Antioxidant.pdf","host_type":""},{"url":"https://doi.org/https://doi.org/10.1016/j.neuint.2015.08.006","host_type":""}],"fields_of_study":["Prion Diseases and Protein Misfolding","Trace Elements in Health","Biochemical effects in animals","0301 basic medicine","0303 health sciences","03 medical and health sciences"],"mesh_terms":["Animals","Antioxidants","Cell Line","Cell Survival","Hydrogen Peroxide","Mice, Inbred C57BL","Mitochondria","Prions","Cell Hypoxia","Apoptosis","Reactive Oxygen Species","Mice, Knockout","Oxidative Stress","Peroxiredoxin VI"],"keywords":["Oxidative stress","Peroxiredoxin","Peroxynitrite","Neuropathology","Cell biology","Oxidative phosphorylation","Biology","Reactive oxygen species","Chemistry","Mitochondrion","Biochemistry","Superoxide","Pathology","Medicine","Peroxidase","Antioxidant","Prion","Astrocytes","Neurodegeneration","Peroxiredoxin 6","Me7","Mice, Knockout","570","Cell Survival","Prions","610","Apoptosis","Hydrogen Peroxide","Antioxidants","Cell Hypoxia","Cell Line","Mitochondria","Mice, Inbred C57BL","Animals","Peroxiredoxin VI"],"sdg_mappings":[{"sdg_number":3,"sdg_label":"3. 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