HSP70-HSP90 Chaperone Networking in Protein-Misfolding Disease

Prodromou, Chrisostomos; Aran-Guiu, Xavi; Oberoi, Jasmeen; Perna, Laura; Chapple, J. Paul; Spuy, Jacqueline van der

doi:10.1007/978-3-031-14740-1_13

Cited by 6 publications

(5 citation statements)

References 268 publications

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“…Formation of this Hsp70-HOP-Hsp90 complex is critical for the activity of the Hsp70-Hsp90 chaperone cycle and correct folding of client proteins. While Hsp70 alone can efficiently fold some substrates, it arrests the folding of other clients due to the highly hydrophobic nature of its substrate-binding chamber [ 98 , 100 ]. To complete their folding, these clients must be transferred from Hsp70 to Hsp90, which highlights the orchestrated activity of these two essential cytoplasmic chaperones.…”

Section: Stip1/hop Proteinmentioning

confidence: 99%

Regulation of Epithelial and Endothelial Barriers by Molecular Chaperones

Lechuga,

Marino-Melendez,

Naydenov

et al. 2024

Cells

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The integrity and permeability of epithelial and endothelial barriers depend on the formation of tight junctions, adherens junctions, and a junction-associated cytoskeleton. The establishment of this junction–cytoskeletal module relies on the correct folding and oligomerization of its protein components. Molecular chaperones are known regulators of protein folding and complex formation in different cellular compartments. Mammalian cells possess an elaborate chaperone network consisting of several hundred chaperones and co-chaperones. Only a small part of this network has been linked, however, to the regulation of intercellular adhesions, and the systematic analysis of chaperone functions at epithelial and endothelial barriers is lacking. This review describes the functions and mechanisms of the chaperone-assisted regulation of intercellular junctions. The major focus of this review is on heat shock protein chaperones, their co-chaperones, and chaperonins since these molecules are the focus of the majority of the articles published on the chaperone-mediated control of tissue barriers. This review discusses the roles of chaperones in the regulation of the steady-state integrity of epithelial and vascular barriers as well as the disruption of these barriers by pathogenic factors and extracellular stressors. Since cytoskeletal coupling is essential for junctional integrity and remodeling, chaperone-assisted assembly of the actomyosin cytoskeleton is also discussed.

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Section: Stip1/hop Proteinmentioning

confidence: 99%

Regulation of Epithelial and Endothelial Barriers by Molecular Chaperones

Lechuga,

Marino-Melendez,

Naydenov

et al. 2024

Cells

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“…Disaggregation and degradation of Aβ 1–40 /Aβ 1–42 and p-Tau proteins are induced by several HSPs [ 28 ]. It has been observed that these proteins are refolded by HSP70 and HSP90, which promote their solubility, induce their breakdown through the proteasome system, and reduce their synthesis [ 35 , 153 , 154 , 155 ]. Moreover, HSC70, HSP90, and HSP70 coordinate to regulate the polymerization of Tau, preventing its clustering [ 28 , 156 , 157 ].…”

Section: Heat Shock Proteins (Hsps) and Epsmentioning

confidence: 99%

Neurodegenerative Proteinopathies Induced by Environmental Pollutants: Heat Shock Proteins and Proteasome as Promising Therapeutic Tools

Moyano,

Sola,

Naval

et al. 2023

Pharmaceutics

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Environmental pollutants’ (EPs) amount and diversity have increased in recent years due to anthropogenic activity. Several neurodegenerative diseases (NDs) are theorized to be related to EPs, as their incidence has increased in a similar way to human EPs exposure and they reproduce the main ND hallmarks. EPs induce several neurotoxic effects, including accumulation and gradual deposition of misfolded toxic proteins, producing neuronal malfunction and cell death. Cells possess different mechanisms to eliminate these toxic proteins, including heat shock proteins (HSPs) and the proteasome system. The accumulation and deleterious effects of toxic proteins are induced through HSPs and disruption of proteasome proteins’ homeostatic function by exposure to EPs. A therapeutic approach has been proposed to reduce accumulation of toxic proteins through treatment with recombinant HSPs/proteasome or the use of compounds that increase their expression or activity. Our aim is to review the current literature on NDs related to EP exposure and their relationship with the disruption of the proteasome system and HSPs, as well as to discuss the toxic effects of dysfunction of HSPs and proteasome and the contradictory effects described in the literature. Lastly, we cover the therapeutic use of developed drugs and recombinant proteasome/HSPs to eliminate toxic proteins and prevent/treat EP-induced neurodegeneration.

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“…The neuroprotective effects of HSF1 as exemplified above can be attributed to the induction and action of a number of molecular chaperones. In this regard, HSP70 and HSP90 are the members of the chaperone family that are analyzed most and whose neuroprotective activity is understood best [69]. Chaperones counteract the toxicity of aggregates using at least three mechanisms: (1) preventing amyloid formation, (2) disaggregating misfolded proteins, and (3) sequestering aggregates to specialized subcellular structures [54].…”

Section: Heat Shock Response and Neuroprotectionmentioning

confidence: 99%

Polyphenols in Inner Ear Neurobiology, Health and Disease: From Bench to Clinics

Osakabe,

Modafferi,

Ontario

et al. 2023

Medicina

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There is substantial experimental and clinical interest in providing effective ways to both prevent and slow the onset of hearing loss. Auditory hair cells, which occur along the basilar membrane of the cochlea, often lose functionality due to age-related biological alterations, as well as from exposure to high decibel sounds affecting a diminished/damaged auditory sensitivity. Hearing loss is also seen to take place due to neuronal degeneration before or following hair cell destruction/loss. A strategy is necessary to protect hair cells and XIII cranial/auditory nerve cells prior to injury and throughout aging. Within this context, it was proposed that cochlea neural stem cells may be protected from such aging and environmental/noise insults via the ingestion of protective dietary supplements. Of particular importance is that these studies typically display a hormetic-like biphasic dose–response pattern that prevents the occurrence of auditory cell damage induced by various model chemical toxins, such as cisplatin. Likewise, the hormetic dose–response also enhances the occurrence of cochlear neural cell viability, proliferation, and differentiation. These findings are particularly important since they confirmed a strong dose dependency of the significant beneficial effects (which is biphasic), whilst having a low-dose beneficial response, whereas extensive exposures may become ineffective and/or potentially harmful. According to hormesis, phytochemicals including polyphenols exhibit biphasic dose–response effects activating low-dose antioxidant signaling pathways, resulting in the upregulation of vitagenes, a group of genes involved in preserving cellular homeostasis during stressful conditions. Modulation of the vitagene network through polyphenols increases cellular resilience mechanisms, thus impacting neurological disorder pathophysiology. Here, we aimed to explore polyphenols targeting the NF-E2-related factor 2 (Nrf2) pathway to neuroprotective and therapeutic strategies that can potentially reduce oxidative stress and inflammation, thus preventing auditory hair cell and XIII cranial/auditory nerve cell degeneration. Furthermore, we explored techniques to enhance their bioavailability and efficacy.

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HSP70-HSP90 Chaperone Networking in Protein-Misfolding Disease

Cited by 6 publications

References 268 publications

Regulation of Epithelial and Endothelial Barriers by Molecular Chaperones

Regulation of Epithelial and Endothelial Barriers by Molecular Chaperones

Neurodegenerative Proteinopathies Induced by Environmental Pollutants: Heat Shock Proteins and Proteasome as Promising Therapeutic Tools

Polyphenols in Inner Ear Neurobiology, Health and Disease: From Bench to Clinics

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