{"doi":"10.1016/j.ibneur.2023.08.2192","title":"APE1/REF-1 MULTIFUNCTIONAL PROTEIN PARADOX IN NEUROLOGICAL DISORDERS","abstract":"Apurinic/Apyrimidinic Endonuclease 1/Redox Effector- 1 (APE1/Ref-1) is a pleotropic protein modulating cellular response to oxidative stress through multiple signaling pathways. We have investigated the expression profile of APE1/Ref-1 in different areas of the central nervous systems (brain and spinal cord). Our studies also shed lights on the specific implication of APE1/Ref-1 redox activity in pain induced by peripheral inflammation after formalin or CFA injection. E3330, a Ref-1 selective inhibitor of the redox activity was co-administered during induction of inflammation in different models. The possible protective effect of curcumin as nutraceutical agent was also tested. We used complementary methods to investigate the implication of altered APE1/Ref-1 levels in spinal cord and brain tissues of rat model during inflammatory episodes. The redox activity of Ref-1 was assessed through its effect on NF-ĸB/Il-6 signaling pathway under inflammation. Moreover, the oxidative stress index, as well as the expression of the key inflammatory markers, was monitored in all groups to follow up the possible role of APE1/Ref-1 in self-healing process. Collectively our research findings reached out the following results: 1- Normal expression and/or differential subcellular distribution of APE1 is essential for neuroprotection as confirmed by the effects of the co-addition of either E3330 or curcumin when compared to induced group. 2- Suppression of NF-kB-Il-6 chronic signaling is central mechanism for tissue healing and neuroprotection. 3- Redox imbalance initiated by neuro-inflammation is halted in response to inhibition of Ref-1 redox activity and re-programmed cellular function toward survival. 4- Organelle and mitochondrial alterations associated with neuro-inflammation were significantly suppressed by APE1-mediated protective mechanism. In conclusion, APE1/Ref-1 is promising therapeutical target as it controls pleotropic signaling pathways with multiple arms at once under cellular stimulation. Exploring mechanisms controlled by this pro-survival protein is crucial for future development of neuro-therapeutic agents. None","journal":"IBRO Neuroscience Reports","year":2023,"id":413655,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9615,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1194921,"name":"Mayssaa M. Wahby","orcid":"0000-0003-0765-8967","position":1,"is_corresponding":false},{"id":1195215,"name":"Mohammad A. Abdulkader","orcid":null,"position":2,"is_corresponding":false},{"id":1170550,"name":"Eman Khaled","orcid":null,"position":3,"is_corresponding":false},{"id":1195216,"name":"Aula Hussein","orcid":null,"position":4,"is_corresponding":false},{"id":1195217,"name":"Samar Harmoush","orcid":null,"position":5,"is_corresponding":false},{"id":1194922,"name":"Marc Landry","orcid":"0000-0003-3936-324X","position":6,"is_corresponding":false},{"id":1194923,"name":"Ahmad Bassiouny","orcid":"0000-0001-8398-1315","position":7,"is_corresponding":false},{"id":1194920,"name":"Amira Zaky","orcid":"0000-0003-4689-4137","position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-19T01:21:57.641539Z","pmid":null,"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":[]}