{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T16:17:43Z","timestamp":1791562663874,"version":"4.3.4"},"reference-count":102,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2024,9,5]],"date-time":"2024-09-05T00:00:00Z","timestamp":1725494400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the Ministry of Science and Higher Education of the Russian Federation","award":["075-15-2023-324"],"award-info":[{"award-number":["075-15-2023-324"]}]},{"name":"NRC \u201cKurchatov Institute\u201d","award":["075-15-2023-324"],"award-info":[{"award-number":["075-15-2023-324"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Neuroinflammation is considered to be one of the driving factors in Parkinson\u2019s disease (PD). This study was conducted using neuronal and glial cell cultures differentiated from induced pluripotent stem cells (iPSC) of healthy donors (HD) and PD patients with different PARK2 mutations (PD). Based on the results of RNA sequencing, qPCR and ELISA, we revealed transcriptional and post-transcriptional changes in HD and PD neurons cultivated in HD and PD glial-conditioned medium. We demonstrated that if one or both of the components of the system, neurons or glia, is Parkin-deficient, the interaction resulted in the down-regulation of a number of key genes related to inflammatory intracellular pathways and negative regulation of apoptosis in neurons, which might be neuroprotective. In PD neurons, the stress-induced up-regulation of APLNR was significantly stronger compared to HD neurons and was diminished by glial soluble factors, both HD and PD. PD neurons in PD glial conditioned medium increased APLN expression and also up-regulated apelin synthesis and release into intracellular fluid, which represented another compensatory action. Overall, the reported results indicate that neuronal self-defense mechanisms contribute to cell survival, which might be characteristic of PD patients with Parkin-deficiency.<\/jats:p>","DOI":"10.3390\/ijms25179621","type":"journal-article","created":{"date-parts":[[2024,9,5]],"date-time":"2024-09-05T05:30:02Z","timestamp":1725514202000},"page":"9621","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Inflammatory Intracellular Signaling in Neurons Is Influenced by Glial Soluble Factors in iPSC-Based Cell Model of PARK2-Associated Parkinson\u2019s Disease"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3858-4561","authenticated-orcid":false,"given":"Tatiana","family":"Gerasimova","sequence":"first","affiliation":[{"name":"Laboratory of Translative Biomedicine, Lopukhin Federal Research and Clinical Center of Physical\u2013Chemical Medicine of Federal Medical Biological Agency, 119435 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7281-4714","authenticated-orcid":false,"given":"Daniil","family":"Poberezhniy","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Neurogenetics and Innate Immunity, National Research Centre \u201cKurchatov Institute\u201d, 123182 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3985-6466","authenticated-orcid":false,"given":"Valentina","family":"Nenasheva","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Neurogenetics and Innate Immunity, National Research Centre \u201cKurchatov Institute\u201d, 123182 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1451-817X","authenticated-orcid":false,"given":"Ekaterina","family":"Stepanenko","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Neurogenetics and Innate Immunity, National Research Centre \u201cKurchatov Institute\u201d, 123182 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Arsenyeva","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Neurogenetics and Innate Immunity, National Research Centre \u201cKurchatov Institute\u201d, 123182 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lyudmila","family":"Novosadova","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Neurogenetics and Innate Immunity, National Research Centre \u201cKurchatov Institute\u201d, 123182 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Igor","family":"Grivennikov","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Neurogenetics and Innate Immunity, National Research Centre \u201cKurchatov Institute\u201d, 123182 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2704-6282","authenticated-orcid":false,"given":"Sergey","family":"Illarioshkin","sequence":"additional","affiliation":[{"name":"Research Center of Neurology, 125367 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9594-1134","authenticated-orcid":false,"given":"Maria","family":"Lagarkova","sequence":"additional","affiliation":[{"name":"Laboratory of Translative Biomedicine, Lopukhin Federal Research and Clinical Center of Physical\u2013Chemical Medicine of Federal Medical Biological Agency, 119435 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vyacheslav","family":"Tarantul","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Neurogenetics and Innate Immunity, National Research Centre \u201cKurchatov Institute\u201d, 123182 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ekaterina","family":"Novosadova","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Neurogenetics and Innate Immunity, National Research Centre \u201cKurchatov Institute\u201d, 123182 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,9,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1038\/s41577-022-00684-6","article-title":"Inflammation and Immune Dysfunction in Parkinson Disease","volume":"22","author":"Tansey","year":"2022","journal-title":"Nat. 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