{"doi":"10.3390/biom15030381","title":"Neurocellular Stress Response to Mojave Type A Rattlesnake Venom: Study of Molecular Mechanisms Using Human iPSC-Derived Neural Stem Cell Model","abstract":"The Mojave rattlesnake venom shows significant geographical variability. The venom of Type A animals primarily contains β-neurotoxin referred to as Mojave Toxin (MTX), which makes bites from this snake particularly feared. We performed a genome-wide transcriptomic analysis of the neurocellular response to Mojave Type A rattlesnake venom using induced pluripotent stem cell-derived neural stem cells to unveil the molecular mechanisms underlying the damage caused by this snake’s envenomation. Our results suggest that snake venom metalloproteases, although having a limited repertoire in Type A venom, facilitate venom spread by digesting the tissue’s extracellular matrix. The MTX, which is composed of heterodimers of basic and acidic phospholipase-A2, co-opts the host arachidonic acid and Ca2+ second messenger mechanisms and triggers multiple signaling cascades, such as the activation of MAPKs and NF-κB-regulated proinflammatory genes; the neurotransmitter overload in excitatory synapses leading to a presynaptic blockade of nerve signals; and the upregulation of unfolded protein response (UPR) due to the depletion of Ca2+ from the endoplasmic reticulum. The upregulated UPR and the oxidative stress caused by reactive oxygen species generated in cytochromeP4501A1-mediated hydroxylation of arachidonic acid contribute to mitochondrial toxicity. The activation of UPR, mitochondrial toxicity, and oxidative stress synergistically contributed to apoptotic and ferroptotic cell death.","journal":"Biomolecules","year":2025,"id":538960,"datarank":0.24034831478168248,"base_score":1.3862943611198906,"endowment":1.3862943611198906,"self_citation_contribution":0.20794415416798362,"citation_network_contribution":0.032404160613698864,"self_endowment_contribution":0.20794415416798362,"citer_contribution":0.032404160613698864,"corpus_percentile":null,"corpus_rank":null,"citation_count":3,"citer_count":3,"citers_with_citation_signal":1,"citers_with_endowment":1,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9618,"is_data_producer":true,"deposit_databanks":{"GEO":["GSE287744"]},"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":366679,"name":"Miriam Aceves","orcid":"0000-0002-1778-0213","position":1,"is_corresponding":false},{"id":956969,"name":"José A. Tapia Granados","orcid":"0000-0003-4101-1024","position":2,"is_corresponding":false},{"id":1426167,"name":"L. García Guerra","orcid":null,"position":3,"is_corresponding":false},{"id":1426168,"name":"Felicia Juarez","orcid":null,"position":4,"is_corresponding":false},{"id":1426169,"name":"Earl Novilla","orcid":null,"position":5,"is_corresponding":false},{"id":424438,"name":"André Cesar Leandro","orcid":"0000-0002-7640-3469","position":6,"is_corresponding":false},{"id":710925,"name":"Marcelo Leandro","orcid":null,"position":7,"is_corresponding":false},{"id":16125,"name":"Juan M. Peralta","orcid":"0000-0002-8811-5579","position":8,"is_corresponding":false},{"id":424440,"name":"Sarah Williams‐Blangero","orcid":"0000-0002-4456-222X","position":9,"is_corresponding":false},{"id":447690,"name":"Elda E. Sánchez","orcid":"0000-0001-5222-8873","position":10,"is_corresponding":false},{"id":675734,"name":"Jacob A. Galán","orcid":"0000-0003-3304-0474","position":11,"is_corresponding":false},{"id":16115,"name":"John Blangero","orcid":"0000-0001-6250-5723","position":12,"is_corresponding":false},{"id":16100,"name":"Joanne E. Curran","orcid":"0000-0002-6898-155X","position":13,"is_corresponding":false},{"id":407791,"name":"Satish Kumar","orcid":"0000-0002-1969-4431","position":0,"is_corresponding":true}],"reference_count":69,"raw_metadata":null,"created_at":"2026-07-19T02:52:25.799399Z","pmid":"40149917","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":[]}