Involvement of heat shock proteins HSP70 in the mechanisms of endogenous neuroprotection: the prospect of using HSP70 modulators

被引:26
|
作者
Belenichev, Igor F. F. [1 ]
Aliyeva, Olena G. G. [2 ]
Popazova, Olena O. O. [3 ]
Bukhtiyarova, Nina V. V. [4 ]
机构
[1] Zaporizhzhia State Med Univ, Dept Pharmacol & Med Formulat Course Normal Physio, Zaporizhzhia, Ukraine
[2] Zaporizhzhia State Med Univ, Dept Med Biol Parasitol & Genet, Zaporizhzhia, Ukraine
[3] Zaporizhzhia State Med Univ, Dept Histol Cytol & Embryol, Zaporizhzhia, Ukraine
[4] Zaporizhzhia State Med Univ, Dept Clin Lab Diagnost, Zaporizhzhia, Ukraine
关键词
heat shock proteins; CNS; ischemia; hypoxia; neuroprotection; HIF-1a; HSP70; modulators; FOCAL CEREBRAL-ISCHEMIA; NF-KAPPA-B; OXIDATIVE STRESS; MOLECULAR CHAPERONES; GLUTATHIONE DISULFIDE; MELATONIN RECEPTORS; THERAPEUTIC TARGET; PROTECTIVE ROLE; BRAIN ISCHEMIA; AMINO-ACIDS;
D O I
10.3389/fncel.2023.1131683
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
This analytical review summarizes literature data and our own research on HSP70-dependent mechanisms of neuroprotection and discusses potential pharmacological agents that can influence HSP70 expression to improve neurological outcomes and effective therapy. The authors formed a systemic concepts of the role of HSP70-dependent mechanisms of endogenous neuroprotection aimed at stopping the formation of mitochondrial dysfunction, activation of apoptosis, desensitization of estrogen receptors, reduction of oxidative and nitrosative stress, prevention of morpho-functional changes in brain cells during cerebral ischemia, and experimentally substantiated new target links for neuroprotection. Heat shock proteins (HSPs) are an evolutionarily integral part of the functioning of all cells acting as intracellular chaperones that support cell proteostasis under normal and various stress conditions (hyperthermia, hypoxia, oxidative stress, radiation, etc.). The greatest curiosity in conditions of ischemic brain damage is the HSP70 protein, as an important component of the endogenous neuroprotection system, which, first of all, performs the function of intracellular chaperones and ensures the processes of folding, holding and transport of synthesized proteins, as well as their degradation, both under normoxic conditions and stress-induced denaturation. A direct neuroprotective effect of HSP70 has been established, which is realized through the regulation the processes of apoptosis and cell necrosis due to a long-term effect on the synthesis of antioxidant enzymes, chaperone activity, and stabilization of active enzymes. An increase in the level of HSP70 leads to the normalization of the glutathione link of the thiol-disulfide system and an increase in the resistance of cells to ischemia. HSP 70 is able to activate and regulate compensatory ATP synthesis pathways during ischemia. It was found that in response to the cerebral ischemia formation, HIF-1a is expressed, which initiates the launch of compensatory mechanisms for energy production. Subsequently, the regulation of these processes switches to HSP70, which "prolongs" the action of HIF-1a, and also independently maintains the expression of mitochondrial NAD-dependent malate dehydrogenase activity, thereby maintaining the activity of the malate-aspartate shuttle mechanism for a long time. During ischemia of organs and tissues, HSP70 performs a protective function, which is realized through increased synthesis of antioxidant enzymes, stabilization of oxidatively damaged macromolecules, and direct anti-apoptotic and mitoprotective action. Such a role of these proteins in cellular reactions during ischemia raises the question of the development of new neuroprotective agents which are able to provide modulation/protection of the genes encoding the synthesis of HSP 70 and HIF-1a proteins. Numerous studies of recent years have noted the important role of HSP70 in the implementation of the mechanisms of metabolic adaptation, neuroplasticity and neuroprotection of brain cells, so the positive modulation of the HSP70 system is a perspective concept of neuroprotection, which can improve the efficiency of the treatment of ischemic-hypoxic brain damage and be the basis for substantiating of the feasibility of using of HSP70 modulators as promising neuroprotectors.
引用
收藏
页数:16
相关论文
共 50 条
  • [11] Heat shock proteins HSP27 and HSP70 in unilateral obstructed kidneys
    Patricia Vallés
    Facundo Jorro
    Liliana Carrizo
    Walter Manucha
    Julio Oliva
    F. Darío Cuello-Carrión
    Daniel R. Ciocca
    Pediatric Nephrology, 2003, 18 : 527 - 535
  • [12] Role of Heat Shock Proteins (HSP70 and HSP90) in Viral Infection
    Lubkowska, Anna
    Pluta, Waldemar
    Stronska, Aleksandra
    Lalko, Alicja
    INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2021, 22 (17)
  • [13] Heat shock proteins HSP70 and HSP60 in Echinococcus granulosus protoscolices
    Martínez, J
    Pérez-Serrano, J
    Bodega, G
    Casado, N
    Rodríguez-Caabeiro, F
    FOLIA PARASITOLOGICA, 1999, 46 (01) : 76 - 78
  • [14] Heat Shock Protein 70 (HSP70) Induction: Chaperonotherapy for Neuroprotection after Brain Injury
    Kim, Jong Youl
    Barua, Sumit
    Huang, Mei Ying
    Park, Joohyun
    Yenari, Midori A.
    Lee, Jong Eun
    CELLS, 2020, 9 (09)
  • [15] HEAT-SHOCK-INDUCED NEUROPROTECTION IS ASSOCIATED WITH GLIAL HSP70 IMMUNOREACTIVITY
    SNIDER, BJ
    CHOI, DW
    NEUROLOGY, 1995, 45 (04) : A199 - A199
  • [16] Heat shock proteins HSP27, HSP60, HSP70, and HSP90
    Lebret, T
    Watson, RWG
    Molinié, V
    O'Neill, A
    Gabriel, C
    Fitzpatrick, JM
    Botto, H
    CANCER, 2003, 98 (05) : 970 - 977
  • [17] Detection of irradiation-induced, membrane heat shock protein 70 (Hsp70) in mouse tumors using Hsp70 Fab fragment
    Stangl, Stefan
    Themelis, George
    Friedrich, Lars
    Ntziachristos, Vasilis
    Sarantopoulos, Athanasios
    Molls, Michael
    Skerra, Arne
    Multhoff, Gabriele
    RADIOTHERAPY AND ONCOLOGY, 2011, 99 (03) : 313 - 316
  • [18] Nitric oxide activates synthesis of heat shock proteins (HSP70)
    Malyshev, IY
    Manukhina, EB
    Malugin, AV
    Mikoyan, VD
    Kubrina, LN
    Vanin, AF
    BIOLOGY OF NITRIC OXIDE, PT 5, 1996, 10 : 108 - 108
  • [19] Understanding Hsp70 phosphorylation using the Hsp70 Chaperone Code array
    Rysbayeva, A.
    Omkar, S.
    Truman, A.
    MOLECULAR BIOLOGY OF THE CELL, 2023, 34 (02) : 1140 - 1140
  • [20] Pharmacological Modulation of Heat Shock Protein 70 (HSP70) - Dependent Mechanisms of Endogenous Neuroprotection in Conditions of Prenatal Chronic Alcoholism by Cerebrocurin and Tiocetam
    Belenichev, Igor F.
    Sokolik, Elena P.
    Bukhtiarova, Nina V.
    Levich, Sergii V.
    KLINIK PSIKOFARMAKOLOJI BULTENI-BULLETIN OF CLINICAL PSYCHOPHARMACOLOGY, 2016, 26 (02): : 103 - 108