medgenМедицинская генетикаMedical Genetics2073-7998Publishing House «Genius Media» LLC10.25557/2073-7998.2026.02.3-16medgen-3390Research ArticleНАУЧНЫЕ ОБЗОРЫREVIEWФармакологическая и генетическая модуляция белков теплового шока: современные подходы и перспективы терапииPharmacological and genetic modulation of heat shock proteins: current approaches and therapeutic perspectivesМусаеваМ. Х.MusaevaM. H.

Мусаева Муъминат Хамидовна

450000, г. Уфа, Россия, ул. Ленина, д. 3

Muxminat H. Musaeva3, Lenina st., Ufa, 450000, Russian Federation

17.muish@mail.ruМеджидовЭ. А.MedzhidovE. A.

450000, г. Уфа, Россия, ул. Ленина, д. 3 

3, Lenina st., Ufa, 450000, Russian Federation

Киянова-ЧарскаяЕ. К.Kiyanova-CharskayaE. K.

197341, г. Санкт-Петербург, Россия, ул. Аккуратова, д. 2

2, Akkuratova st., Saint- Petersburg, 197341, Russian Federation 

ШапловаА. О.ShaplovaA. O.

194100, г. Санкт-Петербург, Россия, ул. Литовская, д. 2

2, Litovskaya st., Saint Petersburg, 194100, Russian Federation 

ВдовинаД. В.VdovinaD. V.

194100, г. Санкт-Петербург, Россия, ул. Литовская, д. 2 

2, Litovskaya st., Saint Petersburg, 194100, Russian Federation

МордасовД. О.MordasovD. O.

191015, г. Санкт-Петербург, Россия, ул. Кирочная, д.41 

41, Kirochnaya st., Saint-Petersburg, 191015, Russian Federation 

ОмаровМ. А.OmarovM. A.

197022, г. Санкт-Петербург, Россия, ул. Льва Толстого, д. 6-8

6-8, Lev Tolstoy st., Saint Petersburg, 197022, Russian Federation

Башкирский Государственный медицинский университет Минздрава РоссииРоссияBashkir state medical university of the Ministry of health of the Russian FederationRussian FederationНациональный медицинский исследовательский центр имени В.А. Алмазова Минздрава РоссииРоссияAlmazov National medical research centre» of the Ministry of Health of the Russian FederationRussian FederationСанкт-Петербургский государственный педиатрический медицинский университет Минздрава РоссииРоссияSaint Petersburg state pediatric medical university” of the Ministry of Health of the Russian FederationRussian FederationСеверо-Западный государственный медицинский университет им. И.И. Мечникова Минздрава РоссииРоссияNorth-Western state medical university named after I.I. Mechnikov of the Ministry of Health of the Russian FederationRussian FederationПервый Санкт-Петербургский государственный медицинский университет имени академика И.П. Павлова Минздрава РоссииРоссияPavlov First Saint Petersburg State Medical University Ministry of Health of the Russian FederationRussian Federation202616032026252316Copyright © Мусаева М.Х., Меджидов Э.А., Киянова-Чарская Е.К., Шаплова А.О., Вдовина Д.В., Мордасов Д.О., Омаров М.А., 20262026Мусаева М.Х., Меджидов Э.А., Киянова-Чарская Е.К., Шаплова А.О., Вдовина Д.В., Мордасов Д.О., Омаров М.А.Musaeva M.H., Medzhidov E.A., Kiyanova-Charskaya E.K., Shaplova A.O., Vdovina D.V., Mordasov D.O., Omarov M.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.medgen-journal.ru/jour/article/view/3390

Молекулярные шапероны, или белки теплового шока (HSP, heat shock proteins), представляют собой консервативный класс белков, отвечающих за правильную укладку полипептидов и предотвращение их неправильного сворачивания и агрегации, тем самым поддерживая клеточный протеостаз. Эти белки классифицируются по молекулярной массе на несколько семейств (включая HSP40, HSP60, HSP70, HSP90, HSP110 и малые HSP) и действуют в координации с ко-шаперонами в качестве центральных компонентов системы клеточного контроля качества белков. Шапероны участвуют во множестве процессов: сворачивание de novo синтезируемых белков, рефолдинг денатурированных или нестабильных белков, сборка белковых комплексов, растворение агрегатов и деградация дефектных полипептидов. Благодаря этим механизмам HSP защищают клетки от стресса (например, теплового удара) и поддерживают гомеостаз белков; активация шаперонного ответа регулируется тепловыми факторами транскрипции (HSF) при стрессовых воздействиях.Дисфункция или дисбаланс активности шаперонов связаны с развитием ряда заболеваний: при нейродегенеративных заболеваниях накопление токсичных белковых агрегатов (таких как амилоид-бета и тау при болезни Альцгеймера) смягчается за счёт работы HSP, а при онкологических заболеваниях чрезмерная экспрессия HSP способствует выживанию и злокачественной прогрессии опухолевых клеток. Учитывая ключевую роль шаперонов, ведутся активные исследования по их таргетной модуляции. Фармакологические ингибиторы HSP90 уже проходят клинические испытания как противоопухолевые препараты, индукторы HSF1/шаперонов и генные стратегии рассматриваются для усиления протеостаза при протеинопатиях. Перспективными направлениями также являются вакцины на основе комплексов HSP–антигенов (использующие шапероны как адъюванты для стимуляции иммунного ответа) и протеостаз-ориентированные терапии, нацеленные на восстановление баланса белкового гомеостаза в клетке.

Molecular chaperones, or heat shock proteins (HSPs), constitute a highly conserved class of proteins responsible for the correct folding of polypeptides and the prevention of their misfolding and aggregation, thereby maintaining cellular proteostasis. These proteins are classified into several families based on molecular weight — including HSP40, HSP60, HSP70, HSP90, HSP110, and small HSPs — and act in coordination with co-chaperones as central components of the cellular protein quality control system. Chaperones participate in numerous cellular processes, including the folding of newly synthesized proteins, refolding of denatured or unstable proteins, assembly of protein complexes, disaggregation, and degradation of defective polypeptides.Through these mechanisms, HSPs protect cells from stress (e.g., heat shock) and support protein homeostasis; activation of the chaperone response is regulated by heat shock transcription factors (HSFs) in response to stress stimuli.Dysfunction or imbalance in chaperone activity is associated with a range of pathologies: in neurodegenerative diseases, the accumulation of toxic protein aggregates (such as amyloid-beta and tau in Alzheimer’s disease) is counteracted by HSP activity, whereas in cancer, the overexpression of HSPs contributes to tumor cell survival and malignant progression. Given their pivotal role, molecular chaperones are actively investigated as targets for therapeutic modulation. Pharmacological inhibitors of HSP90 are currently undergoing clinical trials as anticancer agents, while HSF1/chaperone inducers and gene therapy strategies are being explored to enhance proteostasis in proteinopathies. Promising directions also include vaccines based on HSP–antigen complexes, which utilize chaperones as adjuvants to stimulate immune responses, as well as proteostasis-oriented therapies aimed at restoring protein homeostasis within the cell.

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