inovmedИнновационная медицина КубаниInnovative Medicine of Kuban2541-9897Scientific Research Institute – Ochapovsky Regional Clinical Hospital No. 110.35401/2541-9897-2026-11-2-140-146inovmed-1541Research ArticleОБЗОРЫREVIEWSМолекулярный патогенез синдрома Дауна (трисомии 21)Molecular Pathogenesis of Down Syndrome (Trisomy 21)https://orcid.org/0009-0001-9112-8012ТлехатукЗ. И.TlekhatukZ. I.

Тлехатук Зарина Ильясовна - студент 6-го курса.

Краснодар

Zarina I. Tlekhatuk - 6th-year Student.

Krasnodar

https://orcid.org/0009-0006-8746-3447СутягинаВ. М.SutiaginaV. M.

Сутягина Валерия Михайловна - студент 6-го курса.

Краснодар

Valeria M. Sutiagina - 6th-year Student.

Krasnodar

https://orcid.org/0009-0004-4705-1312ЛинчевскийА. А.LinchevskyA. A.

Линчевский Антон Алексеевич - студент 5-го курса.

Краснодар

Anton A. Linchevsky - .5th-year Student

Krasnodar

https://orcid.org/0009-0003-6783-6371ПушноваА. С.PushnovaA. S.

Пушнова Алиса Станиславовна - студент 5-го курса.

Краснодар

Alisa S. Pushnova - 5th-year Student.

Krasnodar

https://orcid.org/0000-0002-9532-0626ПоляковП. П.PolyakovP. P.

Поляков Павел Павлович - к. м. н., доцент кафедры общей и клинической патологической физиологии.

350063, Краснодар, ул. им. Митрофана Седина, 4

Pavel P. Polyakov - Cand. Sci. (Med.), Associate Professor, Department of General and Clinical Pathological Physiology.

4 Mitrofana Sedina St., Krasnodar, 350063

palpal.p@yandex.ruhttps://orcid.org/0000-0002-5667-0623ЗанинС. А.ZaninS. A.

Занин Сергей Александрович - к. м. н., доцент, и.о. заведующего кафедрой общей и клинической патологической физиологии.

Краснодар

Sergey A. Zanin - Cand. Sci. (Med.), Associate Professor, Acting Head of the Department of General and Clinical Pathologic Physiology.

Krasnodar

https://orcid.org/0000-0002-6203-9272ЦымбаловО. В.TsymbalovO. V.

Цымбалов Олег Владимирович - д. м. н., профессор, профессор кафедры хирургической стоматологии и челюстно-лицевой хирургии.

Краснодар

Oleg V. Tsymbalov - Dr. Sci. (Med.), Professor, Department of Surgical Dentistry and Maxillofacial Surgery.

Krasnodar

https://orcid.org/0009-0005-7731-4520НауменкоД. А.NaumenkoD. A.

Науменко Дарья Антоновна - студент 4-го курса, лечебный факультет.

Краснодар

Daria A. Naumenko - 4th-year Student, Faculty of General Medicine.

Krasnodar

https://orcid.org/0000-0001-8713-325XАхророваМ. Ш.AkhrorovaM. Sh.

Ахророва Малика Шавкатовна - PhD, доцент кафедры детской стоматологии.

Самарканд

Malika Sh. Akhrorova - PhD, Associate Professor, Department of Pediatric Dentistry.

Samarkand

Кубанский государственный медицинский университетРоссияKuban State Medical UniversityRussian FederationСамаркандский государственный медицинский университетРоссияSamarkand State Medical UniversityRussian Federation202622052026112140146Copyright © Тлехатук З.И., Сутягина В.М., Линчевский А.А., Пушнова А.С., Поляков П.П., Занин С.А., Цымбалов О.В., Науменко Д.А., Ахророва М.Ш., 20262026Тлехатук З.И., Сутягина В.М., Линчевский А.А., Пушнова А.С., Поляков П.П., Занин С.А., Цымбалов О.В., Науменко Д.А., Ахророва М.Ш.Tlekhatuk Z.I., Sutiagina V.M., Linchevsky A.A., Pushnova A.S., Polyakov P.P., Zanin S.A., Tsymbalov O.V., Naumenko D.A., Akhrorova M.S.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.innovmedkub.ru/jour/article/view/1541

Синдром Дауна обусловлен врожденной трисомией по хромосоме 21. Основу его патогенеза составляет ряд молекулярных цитопатических эффектов анеуплоидии, активно изучаемых в последнее время.

Цель: Анализ и изложение в виде нарративного обзора молекулярных механизмов негативного влияния на клетку трисомии по хромосоме 21. Первый из них – первичный дисбаланс экспрессии, обусловленный увеличением дозы генов хромосомы 21, и гиперфункция кодируемых ими ферментативных, транспортных, рецепторных, структурных и регуляторных белков. Помимо этого, наличие дополнительной хромосомы влечёт за собой вторичное глобальное нарушение экспрессии, которое обусловлено рядом цитопатических механизмов и приводит к формированию анеуплоидия-ассоциированного фенотипа. Среди данных механизмов рассматриваются проявления протеотоксичности (стехиометрический дисбаланс, перегруженность систем синтеза, фолдинга, посттрансляционных модификаций и деградации, торможение рибосомального биогенеза, активация программ интегрированного ответа на клеточный стресс), нарушение пространственной организации наследственного материала, нестабильность генома (в частности, хромосомная нестабильность), которая сопряжена с накоплением ошибок в разнообразных генах и активацией аутовоспаления.

Down syndrome is attributed to congenital chromosome 21. Its pathogenesis is driven by a range of cytopathic effects associated with aneuploidy, an area that has been the focus of extensive recent investigation.

Objective: To analyze and present, in the form of a narrative review, the molecular mechanisms underlying the detrimental effects of chromosome 21 on the cell. The first of these is a primary imbalance in gene expression caused by increased dosage of chromosome 21 genes and the hyperfunction of the encoded enzymatic, transport, receptor, structural, and regulatory proteins. In addition, the presence of an extra chromosome leads to secondary global dysregulation of gene expression driven by a range of cytopathic mechanisms, resulting in the development of an aneuploidy-associated phenotype. Among these mechanisms are features of proteotoxicity (stoichiometric imbalance; overload of the systems responsible for protein synthesis, folding, post-translational modifications, and degradation; inhibition of ribosomal biogenesis; and activation of integrated cellular stress response programs), disruption of the spatial organization of genetic material, and genome instability (in particular chromosomal instability), which is associated with the accumulation of errors in a wide range of genes and activation of autoinflammatory processes.

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The authors declare that there are no conflicts of interest present.