{"doi":"10.1073/pnas.2301534120","title":"Aberrant DJ-1 expression underlies L-type calcium channel hypoactivity in dendrites in tuberous sclerosis complex and Alzheimer’s disease","abstract":"L-type voltage-gated calcium (Ca 2+ ) channels (L-VGCC) dysfunction is implicated in several neurological and psychiatric diseases. While a popular therapeutic target, it is unknown whether molecular mechanisms leading to disrupted L-VGCC across neurodegenerative disorders are conserved. Importantly, L-VGCC integrate synaptic signals to facilitate a plethora of cellular mechanisms; however, mechanisms that regulate L-VGCC channel density and subcellular compartmentalization are understudied. Herein, we report that in disease models with overactive mammalian target of rapamycin complex 1 (mTORC1) signaling (or mTORopathies), deficits in dendritic L-VGCC activity are associated with increased expression of the RNA-binding protein (RBP) Parkinsonism-associated deglycase (DJ-1). DJ-1 binds the mRNA coding for the alpha and auxiliary Ca 2+ channel subunits Ca V 1.2 and α2δ2, and represses their mRNA translation, only in the disease states, specifically preclinical models of tuberous sclerosis complex (TSC) and Alzheimer’s disease (AD). In agreement, DJ-1-mediated repression of Ca V 1.2/α2δ2 protein synthesis in dendrites is exaggerated in mouse models of AD and TSC, resulting in deficits in dendritic L-VGCC calcium activity. Finding of DJ-1-regulated L-VGCC activity in dendrites in TSC and AD provides a unique signaling pathway that can be targeted in clinical mTORopathies.","journal":"Proceedings of the National Academy of Sciences","year":2023,"id":343508,"datarank":0.40620753016533157,"base_score":2.70805020110221,"endowment":2.70805020110221,"self_citation_contribution":0.40620753016533157,"citation_network_contribution":0.0,"self_endowment_contribution":0.40620753016533157,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":14,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9461,"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":583565,"name":"Ayse Uneri","orcid":"0000-0002-9303-8184","position":1,"is_corresponding":false},{"id":584013,"name":"Colin J. McArdle","orcid":null,"position":2,"is_corresponding":false},{"id":364530,"name":"Zhiyong Deng","orcid":"0000-0001-9761-9720","position":3,"is_corresponding":false},{"id":1081104,"name":"Hailey X. Egido-Betancourt","orcid":"0000-0002-6579-2411","position":4,"is_corresponding":false},{"id":575824,"name":"Luisa P. Cacheaux","orcid":"0000-0001-7428-3355","position":5,"is_corresponding":false},{"id":583566,"name":"Sanjeev V. Namjoshi","orcid":"0000-0002-6648-3434","position":6,"is_corresponding":false},{"id":576562,"name":"William C. Taylor","orcid":null,"position":7,"is_corresponding":false},{"id":583567,"name":"Xin Wang","orcid":"0000-0002-2184-3328","position":8,"is_corresponding":false},{"id":726874,"name":"Samuel H. Barth","orcid":"0000-0003-4823-3076","position":9,"is_corresponding":false},{"id":584014,"name":"Cameron Reynoldson","orcid":null,"position":10,"is_corresponding":false},{"id":584015,"name":"Juan Penaranda","orcid":null,"position":11,"is_corresponding":false},{"id":1081507,"name":"Michael P. Stierer","orcid":null,"position":12,"is_corresponding":false},{"id":801008,"name":"Chelcie F. Heaney","orcid":"0000-0001-7712-1052","position":13,"is_corresponding":false},{"id":55001,"name":"Suzanne Craft","orcid":"0000-0003-0591-8657","position":14,"is_corresponding":false},{"id":38380,"name":"C. Dirk Keene","orcid":"0000-0002-5291-1469","position":15,"is_corresponding":false},{"id":285815,"name":"Tao Ma","orcid":"0000-0002-0763-7261","position":16,"is_corresponding":false},{"id":575825,"name":"Kimberly F. Raab‐Graham","orcid":"0000-0001-6502-057X","position":17,"is_corresponding":false},{"id":575823,"name":"Farr Niere","orcid":"0000-0003-0287-0889","position":0,"is_corresponding":true}],"reference_count":72,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T01:11:21.758449Z","pmid":"37903257","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":[]}