Acta NaturaeActa NaturaeActa Naturae2075-8251Acta Naturae Ltd2766410.32607/actanaturae.27664Research ArticlesЭкспериментальные статьиResearch ArticleReduced expression of immune response genes in neural cells with mutations in the PARK2 gene in Parkinson’s diseaseПри болезни Паркинсона в нейральных клетках с мутациями в PARK2 снижается экспрессия генов иммунного ответаFedoseyevaV. B.ФедосееваВ. Б.
Russian Federation
fedoseeva_VB@nrcki.ruNovosadovaE. V.НовосадоваЕ. В.
Russian Federation
fedoseeva_VB@nrcki.ruNenashevaV. V.НенашеваВ. В.
Russian Federation
fedoseeva_VB@nrcki.ruNovosadovaL. V.НовосадоваЛ. В.
Russian Federation
fedoseeva_VB@nrcki.ruGrivennikovI. A.ГривенниковИ. А.
Russian Federation
fedoseeva_VB@nrcki.ruTarantulV. Z.ТарантулВ. З.
Russian Federation
fedoseeva_VB@nrcki.ruNational Research Center “Kurchatov Institute”Национальный исследовательский центр «Курчатовский институт»Federal Research and Clinical Center for Physicochemical Medicine named after Academician Yu.M. Lopukhin, Federal Medical and Biological AgencyФГБУ Федеральный научно-клинический центр физико-химической медицины имени академика Ю.М. Лопухина Федерального медико-биологического агентства220420261811041132703202517092025Copyright ©; 2026, Fedoseyeva V.B., Novosadova E.V., Nenasheva V.V., Novosadova L.V., Grivennikov I.A., Tarantul V.Z.Copyright ©; 2026, Федосеева В.Б., Новосадова Е.В., Ненашева В.В., Новосадова Л.В., Гривенников И.А., Тарантул В.З.2026Fedoseyeva V.B., Novosadova E.V., Nenasheva V.V., Novosadova L.V., Grivennikov I.A., Tarantul V.Z.Федосеева В.Б., Новосадова Е.В., Ненашева В.В., Новосадова Л.В., Гривенников И.А., Тарантул В.З.https://creativecommons.org/licenses/by/4.0https://actanaturae.ru/2075-8251/article/view/27664

Parkinson’s disease (PD) is one of the most common chronic neurodegenerative diseases. PD is characterized by the dysfunction of multiple body functions caused by changes in the expression of a large number of genes. Current evidence suggests that changes in the innate immunity and neuroinflammation may play an important role in the pathogenesis of the disease. However, the exact mechanism through which immune dysfunction develops in the context of PD pathogenesis remains unclear. In this study, with the use of transcriptome sequencing (RNA-seq), followed by quantitative PCR, we managed to detect a differential expression of the genes involved in the immune activity in neural progenitors (NPs) and glial cells derived from induced pluripotent stem cells from healthy donors (HDs) and PD patients carrying mutations in the PARK2 gene. Expression of many of the genes involved in a number of innate immune signaling pathways (in particular, in the canonical NFκB, non-canonical NFκB, the TNFα/NFκB, IL6/STAT3, IL2/STAT5 pathways, as well as the IFNγ and IFNα response) in cells from PD patients was found to be reduced compared to that in the cells from healthy donors. A mechanism for regulating these signaling pathways in the neural precursors of PD patients carrying mutations in the PARK2 gene is proposed.

Болезнь Паркинсона (БП) – одно из наиболее распространенных хронических нейродегенеративных заболеваний. При БП наблюдаются изменения в экспрессии большого числа генов, что приводит к нарушению различных функций организма. Опубликованы данные, свидетельствующие о важной роли изменений в системе врожденного иммунитета и нейровоспаления в патогенезе этого заболевания. Однако точный механизм нарушения иммунного ответа в контексте патогенеза БП изучен далеко не полностью. В настоящей работе с помощью секвенирования транскриптома (RNA-seq) с последующей количественной ПЦР обнаружена дифференциальная экспрессия генов, связанных с иммунным ответом, в клетках нейральных предшественников и глии, полученных из индуцированных плюрипотентных стволовых клеток здоровых доноров и пациентов с БП, несущих мутации в гене PARK2. В клетках от пациентов с БП по сравнению с клетками здоровых доноров понижена экспрессия множества генов, участвующих в ряде сигнальных путей врожденного иммунитета, в частности, в каноническом пути NFκB, неканоническом NFκB, TNFα/NFκB, IL6–STAT3, IL2–STAT5 и в ответах IFNγ и IFNα. Предложен механизм регуляции данных сигнальных путей в клетках нейральных предшественников у пациентов с БП с мутациями в гене PARK2.

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