{"doi":"10.1016/j.neurobiolaging.2023.09.008","title":"Protein retention in the endoplasmic reticulum rescues Aβ toxicity in Drosophila","abstract":"Amyloid β (Aβ) accumulation is a hallmark of Alzheimer's disease. In adult Drosophila brains, human Aβ overexpression harms climbing and lifespan. It's uncertain whether Aβ is intrinsically toxic or activates downstream neurodegeneration pathways. Our study uncovers a novel protective role against Aβ toxicity: intra-endoplasmic reticulum (ER) protein accumulation with a focus on laminin and collagen subunits. Despite high Aβ, laminin B1 (LanB1) overexpression robustly counters toxicity, suggesting a potential Aβ resistance mechanism. Other laminin subunits and collagen IV also alleviate Aβ toxicity; combining them with LanB1 augments the effect. Imaging reveals ER retention of LanB1 without altering Aβ secretion. LanB1's rescue function operates independently of the IRE1α/XBP1 ER stress response. ER-targeted GFP overexpression also mitigates Aβ toxicity, highlighting broader ER protein retention advantages. Proof-of-principle tests in murine hippocampal slices using mouse Lamb1 demonstrate ER retention in transduced cells, indicating a conserved mechanism. Though ER protein retention generally harms, it could paradoxically counter neuronal Aβ toxicity, offering a new therapeutic avenue for Alzheimer's disease.","journal":"Neurobiology of Aging","year":2023,"id":362887,"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":0.9524,"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":417550,"name":"Lucy J. Minkley","orcid":"0000-0002-3432-0032","position":1,"is_corresponding":false},{"id":818456,"name":"Salomé Aspe","orcid":null,"position":2,"is_corresponding":false},{"id":817735,"name":"Sebastian Judd-Mole","orcid":"0000-0003-0171-5246","position":3,"is_corresponding":false},{"id":817736,"name":"Sofia Moura","orcid":"0000-0002-9000-2290","position":4,"is_corresponding":false},{"id":471542,"name":"Miranda C. Dyson","orcid":"0000-0003-0845-662X","position":5,"is_corresponding":false},{"id":418942,"name":"Arjunan Rajasingam","orcid":null,"position":6,"is_corresponding":false},{"id":417549,"name":"Nathaniel S. Woodling","orcid":"0000-0002-0298-3800","position":7,"is_corresponding":false},{"id":697846,"name":"Magda L. Atilano","orcid":"0000-0002-3819-2023","position":8,"is_corresponding":false},{"id":818457,"name":"Mumtaz Ahmad","orcid":null,"position":9,"is_corresponding":false},{"id":817737,"name":"Claire S. Durrant","orcid":"0000-0001-7552-7358","position":10,"is_corresponding":false},{"id":339603,"name":"Tara L. Spires‐Jones","orcid":"0000-0003-2530-0598","position":11,"is_corresponding":false},{"id":262161,"name":"Linda Partridge","orcid":"0000-0001-9615-0094","position":12,"is_corresponding":false},{"id":817734,"name":"James H. Catterson","orcid":"0000-0003-4231-0114","position":0,"is_corresponding":true}],"reference_count":106,"raw_metadata":null,"created_at":"2026-07-19T01:14:23.749325Z","pmid":"37837732","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":[]}