{"doi":"10.26508/lsa.202101193","title":"Testing of the therapeutic efficacy and safety of AMPA receptor RNA aptamers in an ALS mouse model","abstract":"In motor neurons of sporadic amyotrophic lateral sclerosis (ALS) patients, the RNA editing at the glutamine/arginine site of the GluA2 subunit of α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors is defective or incomplete. As a result, AMPA receptors containing the abnormally expressed, unedited isoform of GluA2 are highly Ca 2+ -permeable, and are responsible for mediating abnormal Ca 2+ influx, thereby triggering motor neuron degeneration and cell death. Thus, blocking the AMPA receptor–mediated, abnormal Ca 2+ influx is a potential therapeutic strategy for treatment of sporadic ALS. Here, we report a study of the efficacy and safety of two RNA aptamers targeting AMPA receptors on the ALS phenotype of AR2 mice. A 12-wk continuous, intracerebroventricular infusion of aptamers to AR2 mice reduced the progression of motor dysfunction, normalized TDP-43 mislocalization, and prevented death of motor neurons. Our results demonstrate that the use of AMPA receptor aptamers as a novel class of AMPA receptor antagonists is a promising strategy for developing an ALS treatment approach.","journal":"Life Science Alliance","year":2022,"id":284482,"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":5,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9621,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":962723,"name":"Takenari Yamashita","orcid":null,"position":1,"is_corresponding":false},{"id":962724,"name":"Sayaka Teramoto","orcid":null,"position":2,"is_corresponding":false},{"id":324006,"name":"Zhen Huang","orcid":"0000-0002-8640-3227","position":3,"is_corresponding":false},{"id":431519,"name":"Janet Lynch","orcid":null,"position":4,"is_corresponding":false},{"id":17442,"name":"Tatsushi Toda","orcid":"0000-0002-0717-1123","position":5,"is_corresponding":false},{"id":430837,"name":"Li Niu","orcid":"0000-0002-0917-9663","position":6,"is_corresponding":false},{"id":962254,"name":"Shin Kwak","orcid":"0000-0002-9936-6664","position":7,"is_corresponding":false},{"id":962253,"name":"Megumi Akamatsu","orcid":"0000-0002-6893-805X","position":0,"is_corresponding":true}],"reference_count":49,"raw_metadata":null,"created_at":"2026-07-19T00:29:36.828109Z","pmid":"35022247","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":[]}