{"doi":"10.1016/j.stemcr.2025.102535","title":"Telmisartan is neuroprotective in a hiPSC-derived spinal microtissue model for C9orf72 ALS via inhibition of neuroinflammation","abstract":"Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive motor neuron (MN) loss. The most common genetic cause, a hexanucleotide repeat expansion in C9orf72 (C9-ALS), disrupts microglial function, contributing to neuroinflammation, a key disease driver. To investigate this, we developed a three-dimensional spinal microtissue (SM) model incorporating human induced pluripotent stem cell (hiPSC)-derived MNs, astrocytes, and microglia. Screening 190 Food and Drug Administration (FDA)-approved compounds, we identified sartans-angiotensin II receptor I blockers (ARBs)-as potent inhibitors of neuroinflammation. Telmisartan, a highly brain-penetrant ARB, significantly reduced the levels of pro-inflammatory cytokines interleukin (IL)-6 and IL-8 and rescued MN loss in C9-ALS SMs. Our findings suggest that C9-ALS microglia drive MN toxicity and that telmisartan can effectively mitigate inflammation and preserve MN viability. This work lays the groundwork for modeling disease-related neuroinflammation and points to telmisartan as a therapeutic candidate worth further exploration for treating C9-ALS.","journal":"Stem Cell Reports","year":2025,"id":517509,"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":8,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9476,"is_data_producer":false,"deposit_databanks":null,"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":1383819,"name":"Björn F. Vahsen","orcid":"0000-0002-5159-5070","position":1,"is_corresponding":false},{"id":1383820,"name":"Mario Ledesma-Terrón","orcid":"0000-0003-4045-3939","position":2,"is_corresponding":false},{"id":618828,"name":"Zhuoning Li","orcid":"0009-0005-9064-8170","position":3,"is_corresponding":false},{"id":1384447,"name":"Laura Tuffery","orcid":null,"position":4,"is_corresponding":false},{"id":1205641,"name":"Nan Xu","orcid":"0000-0003-4642-2877","position":5,"is_corresponding":false},{"id":384603,"name":"Elizabeth L. Calder","orcid":null,"position":6,"is_corresponding":false},{"id":678633,"name":"Johannes Jungverdorben","orcid":"0000-0002-7227-1139","position":7,"is_corresponding":false},{"id":1327017,"name":"Leslie Weber","orcid":"0000-0003-1187-7812","position":8,"is_corresponding":false},{"id":510340,"name":"Aaron Zhong","orcid":"0000-0002-2468-0923","position":9,"is_corresponding":false},{"id":1383821,"name":"David G. Míguez","orcid":"0000-0001-8065-1142","position":10,"is_corresponding":false},{"id":938124,"name":"Mara Monetti","orcid":"0009-0006-9778-9010","position":11,"is_corresponding":false},{"id":291183,"name":"Ting Zhou","orcid":"0000-0003-1423-1507","position":12,"is_corresponding":false},{"id":849589,"name":"Elisa Giacomelli","orcid":"0000-0001-9233-235X","position":13,"is_corresponding":false},{"id":109231,"name":"Lorenz Studer","orcid":"0000-0003-0741-7987","position":14,"is_corresponding":false},{"id":255097,"name":"Berkiye Sonustun","orcid":"0000-0002-1403-6931","position":0,"is_corresponding":true}],"reference_count":47,"raw_metadata":null,"created_at":"2026-07-19T02:48:59.410472Z","pmid":"40541176","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":[]}