{"doi":"10.17615/52jy-a288","title":"Bcl-2 enhances Ca2+ signaling to support the intrinsic regenerative capacity of CNS axons","abstract":"At a certain point in development, axons in the mammalian CNS undergo a profound loss of intrinsic growth capacity, which leads to poor regeneration after injury. Overexpression of Bcl-2 prevents this loss, but the molecular basis of this effect remains unclear. Here, we report that Bcl-2 supports axonal growth by enhancing intracellular Ca2+ signaling and activating cAMP response element binding protein (CREB) and extracellular-regulated kinase (Erk), which stimulate the regenerative response and neuritogenesis. Expression of Bcl-2 decreases endoplasmic reticulum (ER) Ca2+ uptake and storage, and thereby leads to a larger intracellular Ca2+ response induced by Ca2+ influx or axotomy in Bcl-2-expressing neurons than in control neurons. Bcl-xL, an antiapoptotic member of the Bcl-2 family that does not affect ER Ca2+ uptake, supports neuronal survival but cannot activate CREB and Erk or promote axon regeneration. These results suggest a novel role for ER Ca2+ in the regulation of neuronal response to injury and define a dedicated signaling event through which Bcl-2 supports CNS regeneration.","journal":"UNC Libraries","year":2020,"id":116143,"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":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9515,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":393820,"name":"William D. Snider","orcid":null,"position":1,"is_corresponding":false},{"id":543870,"name":"Jianwei Jiao","orcid":"0000-0002-7893-0721","position":2,"is_corresponding":false},{"id":374981,"name":"Darlene A. Dartt","orcid":"0000-0002-0576-6932","position":3,"is_corresponding":false},{"id":544495,"name":"Xizhong Huang","orcid":null,"position":4,"is_corresponding":false},{"id":543871,"name":"Dongfeng Chen","orcid":"0000-0003-1263-2374","position":5,"is_corresponding":false},{"id":196885,"name":"Rachael L. Neve","orcid":null,"position":6,"is_corresponding":false},{"id":544494,"name":"Rachel Ann Feit-Leithman","orcid":null,"position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-18T23:13:44.286758Z","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":[]}