{"doi":"10.1101/2021.06.03.446965","title":"Lack of p62 impairs glycogen aggregation and exacerbates pathology in a mouse model of myoclonic epilepsy of Lafora","abstract":"ABSTRACT Background Lafora disease (LD) is a fatal childhood-onset dementia characterized by the extensive accumulation of glycogen aggregates—the so-called Lafora Bodies (LBs)—in several organs. The accumulation of LBs in the brain underlies the neurological phenotype of the disease. LBs are composed of abnormal glycogen and various associated proteins, including p62, an autophagy adaptor that participates in the aggregation and clearance of misfolded proteins. Methods To study the role of p62 in the formation of LBs and its participation in the pathology of LD, we generated a mouse model of the disease (malin KO ) lacking p62. Results Deletion of p62 prevented LB accumulation in skeletal muscle and cardiac tissue. In the brain, the absence of p62 altered LB morphology and increased susceptibility to epilepsy. Conclusions These results demonstrate that p62 participates in the formation of LBs and suggest that the sequestration of abnormal glycogen into LBs is a protective mechanism through which to reduce the deleterious consequences of its accumulation in the brain.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2021,"id":220978,"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":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9607,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":679721,"name":"Arnau Hervera","orcid":"0000-0001-8362-369X","position":1,"is_corresponding":false},{"id":487689,"name":"Olga Varea","orcid":null,"position":2,"is_corresponding":false},{"id":475509,"name":"M. Kathryn Brewer","orcid":"0000-0001-5089-3570","position":3,"is_corresponding":false},{"id":679722,"name":"Iliana López‐Soldado","orcid":"0000-0001-5890-6073","position":4,"is_corresponding":false},{"id":820694,"name":"Anna Guitart-Solanes","orcid":"0000-0003-2110-6990","position":5,"is_corresponding":false},{"id":486910,"name":"Mònica Aguilera","orcid":"0000-0003-0763-7947","position":6,"is_corresponding":false},{"id":821065,"name":"Neus Prat","orcid":null,"position":7,"is_corresponding":false},{"id":679723,"name":"José Antonio del Rı́o","orcid":"0000-0002-5214-4909","position":8,"is_corresponding":false},{"id":486912,"name":"Joan J. Guinovart","orcid":"0000-0003-0770-9592","position":9,"is_corresponding":false},{"id":486909,"name":"Jordi Durán","orcid":"0000-0002-8342-4882","position":10,"is_corresponding":false},{"id":287584,"name":"Pasquale Pellegrini","orcid":"0000-0002-6196-4191","position":0,"is_corresponding":true}],"reference_count":68,"raw_metadata":null,"created_at":"2026-07-18T23:53:50.838581Z","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":[]}