{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T05:50:25Z","timestamp":1787637025518,"version":"build-2736575974"},"reference-count":57,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2021,2,10]],"date-time":"2021-02-10T00:00:00Z","timestamp":1612915200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Cognitive dysfunction and mood changes are prevalent and especially taxing issues for patients with systemic lupus erythematosus (SLE). Tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) and its cognate receptor Fn14 have been shown to play an important role in neurocognitive dysfunction in murine lupus. We profiled and compared gene expression in the cortices of MRL\/+, MRL\/lpr (that manifest lupus-like phenotype) and MRL\/lpr-Fn14 knockout (Fn14ko) adult female mice to determine the transcriptomic impact of TWEAK\/Fn14 on cortical gene expression in lupus. We found that the TWEAK\/Fn14 pathway strongly affects the expression level, variability and coordination of the genomic fabrics responsible for neurotransmission and chemokine signaling. Dysregulation of the Phosphoinositide 3-kinase (PI3K)-AKT pathway in the MRL\/lpr lupus strain compared with the MRL\/+ control and Fn14ko mice was particularly prominent and, therefore, promising as a potential therapeutic target, although the complexity of the transcriptomic fabric highlights important considerations in in vivo experimental models.<\/jats:p>","DOI":"10.3390\/genes12020251","type":"journal-article","created":{"date-parts":[[2021,2,12]],"date-time":"2021-02-12T00:49:26Z","timestamp":1613090966000},"page":"251","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Remodeling of Neurotransmission, Chemokine, and PI3K-AKT Signaling Genomic Fabrics in Neuropsychiatric Systemic Lupus Erythematosus"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9700-6537","authenticated-orcid":false,"given":"Dumitru","family":"Iacobas","sequence":"first","affiliation":[{"name":"Center for Computational Systems Biology, Personalized Genomics Laboratory, Roy G. Perry College of Engineering, Prairie View A &amp; M University, Prairie View, TX 77446, USA"},{"name":"DP Purpura Department of Neuroscience, Albert Einstein College of Medicine, Bronx, NY 10461, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Wen","sequence":"additional","affiliation":[{"name":"Department of Medicine (Rheumatology), Albert Einstein College of Medicine, Bronx, NY 10461, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanda","family":"Iacobas","sequence":"additional","affiliation":[{"name":"Department of Pathology, New York Medical College, Valhalla, NY 10595, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5577-3196","authenticated-orcid":false,"given":"Noa","family":"Schwartz","sequence":"additional","affiliation":[{"name":"Department of Medicine (Rheumatology), Albert Einstein College of Medicine, Bronx, NY 10461, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chaim","family":"Putterman","sequence":"additional","affiliation":[{"name":"Department of Medicine (Rheumatology), Albert Einstein College of Medicine, Bronx, NY 10461, USA"},{"name":"Department of Microbiology &amp; Immunology, Albert Einstein College of Medicine, Bronx, NY 10461, USA"},{"name":"Azrieli Faculty of Medicine, Bar-Ilan University, Zefat 52100, Israel"},{"name":"Galilee Medical Center, Research Institute, Nahariya 22100, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,2,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1413","DOI":"10.1002\/art.40933","article-title":"Cognitive dysfunction in systemic lupus erythematosus: A case for initiating trials","volume":"71","author":"Kello","year":"2019","journal-title":"Arthritis Rheumatol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1002\/1529-0131(199904)42:4<599::AID-ANR2>3.0.CO;2-F","article-title":"The American College of Rheumatology nomenclature and case definitions for neuropsychiatric lupus syndromes","volume":"42","author":"Liang","year":"1999","journal-title":"Arthritis Rheumatol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1038\/s41584-018-0156-8","article-title":"Neuropsychiatric lupus: New mechanistic insights and future treatment directions","volume":"15","author":"Schwartz","year":"2019","journal-title":"Nat. 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