The Chemical Inhibitors of Endocytosis: From Mechanisms to Potential Clinical Applications

Szewczyk-Roszczenko, Olga Klaudia; Roszczenko, Piotr; Shmakova, Anna; Finiuk, Nataliya; Holota, Serhii; Lesyk, Roman; Bielawska, Anna; Vassetzky, Yegor; Bielawski, Krzysztof

doi:10.3390/cells12182312

Cited by 19 publications

(9 citation statements)

References 245 publications

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“…And the results showed that the significantly enriched pathways were the Endocytosis pathway, suggesting that PLGA-RES are fully internalized by endocytosis like most other NPs. Previous study indicated that polymer-based NPs mostly enter the cell via Clathrin-mediated endocytosis based on binding of β-arrestin and G protein-coupled receptors (GPCRs) ( Zhang et al, 2020 ; Janetzko et al, 2022 ; Szewczyk-Roszczenko et al, 2023 ; Wess et al, 2023 ). In the present study, we found that the expression of ARRB2 was restored in vitrified oocytes after PLGA-RES NPs treatment.…”

Section: Discussionmentioning

confidence: 99%

Superior performance of biocomposite nanoparticles PLGA-RES in protecting oocytes against vitrification stimuli

Hai,

Bai,

Liu

et al. 2024

Front. Bioeng. Biotechnol.

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Irreversible cryogenic damage caused by oocyte vitrification limits its widespread use in female fertility preservation. In recent years, nanoparticles (NPs) have gained great attention as potential alternatives in protecting oocytes against cryoinjuries. In this paper, a novel composite nanoparticle, poly (lactic-co-glycolic acid)-resveratrol (PLGA-RES) was designed to improve the biocompatibility and sustained release properties by encapsulating natural antioxidant RES into PLGA NPs. Firstly, biotoxicity and oxidation resistance of PLGA-RES were determined, and the results showed that PLGA-RES had nontoxic effect on oocyte survival during in vitro maturation (IVM) (97.08% ± 0.24% vs. 98.89% ± 1.11%, p > 0.05). Notably, PLGA-RES even increased maturation (65.10% ± 4.11% vs. 52.85% ± 2.87%, p < 0.05) and blastocyst rate (56.13% ± 1.36% vs. 40.91% ± 5.85%, p < 0.05). Moreover, the reduced reactive oxygen species (ROS) level (13.49 ± 2.30 vs. 34.07 ± 3.30, p < 0.01), increased glutathione (GSH) (44.13 ± 1.57 vs. 37.62 ± 1.79, p < 0.01) and elevated mitochondrial membrane potential (MMP) levels (43.10 ± 1.81 vs. 28.52 ± 1.25, p < 0.01) were observed in oocytes treated with PLGA-RES when compared with that of the control group. Subsequently, the role of PLGA-RES played in oocytes during vitrification was systematically evaluated. The results showed that the addition of PLGA-RES during vitrification and thawing significantly improved the survival rate (80.42% ± 1.97% vs. 75.37% ± 1.3%, p < 0.05). Meanwhile, increased GSH (15.09 ± 0.86 vs. 14.51 ± 0.78, p < 0.01) and mitochondrial membrane potential (22.56 ± 3.15 vs. 6.79 ± 0.60, p < 0.01), decreased reactive oxygen species levels (52.11 ± 2.95 vs. 75.41 ± 7.23, p < 0.05) and reduced mitochondrial abnormality distribution rate (25.00% ± 0.29% vs. 33.33% ± 1.15%, p < 0.01) were assessed in vitrified MII oocytes treated with PLGA-RES. Furthermore, transcriptomic analyses demonstrated that PLGA-RES participated in endocytosis and PI3K/AKT/mTOR pathway regulation, which was verified by the rescued expression of ARRB2 and ULK3 protein after PLGA-RES treatment. In conclusion, PLGA-RES exhibited potent antioxidant activity, and could be used as an efficacious strategy to improve the quality of vitrified oocytes.

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Section: Discussionmentioning

confidence: 99%

Superior performance of biocomposite nanoparticles PLGA-RES in protecting oocytes against vitrification stimuli

Hai,

Bai,

Liu

et al. 2024

Front. Bioeng. Biotechnol.

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“…11,18 To confirm this, a fluorescently labeled Tat-derived cell-penetrating peptide (Tat CPP-Cy5) was used. Cells were first pretreated or not (control) for 1 h with genistein, an inhibitor of endocytosis, 19 and then Tat CPP-Cy5 was added to cell medium for 30 min followed by extensive cell wash and subsequent analysis of Tat CPP-Cy5 cellular and nuclear penetration (Supporting Information S6: Figure 7). The addition of genistein drastically inhibited Tat CPP-Cy5 penetration in cells (Supporting Information S6: Figure 7).…”

Section: Hiv-1 Tat Decreased Hla-dr Expression In Cultured B Cellsmentioning

confidence: 99%

Chronic HIV‐1 Tat action induces HLA‐DR downregulation in B cells: A mechanism for lymphoma immune escape in people living with HIV

Shmakova,

Hugot,

Kozhevnikova

et al. 2024

Journal of Medical Virology

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Despite the success of combination antiretroviral therapy, people living with human immunodeficiency virus (HIV) still have an increased risk of Epstein−Barr virus (EBV)‐associated B cell malignancies. In the HIV setting, B cell physiology is altered by coexistence with HIV‐infected cells and the chronic action of secreted viral proteins, for example, HIV‐1 Tat that, once released, efficiently penetrates noninfected cells. We modeled the chronic action of HIV‐1 Tat on B cells by ectopically expressing Tat or TatC22G mutant in two lymphoblastoid B cell lines. The RNA‐sequencing analysis revealed that Tat deregulated the expression of hundreds of genes in B cells, including the downregulation of a subset of major histocompatibility complex (MHC) class II‐related genes. Tat‐induced downregulation of HLA‐DRB1 and HLA‐DRB5 genes led to a decrease in HLA‐DR surface expression; this effect was reproduced by coculturing B cells with Tat‐expressing T cells. Chronic Tat presence decreased the NF‐ᴋB pathway activity in B cells; this downregulated NF‐ᴋB‐dependent transcriptional targets, including MHC class II genes. Notably, HLA‐DRB1 and surface HLA‐DR expression was also decreased in B cells from people with HIV. Tat‐induced HLA‐DR downregulation in B cells impaired EBV‐specific CD4+ T cell response, which contributed to the escape from immune surveillance and could eventually promote B cell lymphomagenesis in people with HIV.

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“…As discussed within this review, there is abundant evidence that CME is a potential early disease modifier of AD in neurons, astrocytes, and microglia upstream of endolysosomal involvement. There have been several clinical trials evaluating endocytosis inhibitors which specifically block CME to treat coronavirus infection ( Szewczyk-Roszczenko et al, 2023 ). These inhibitors include Ruxolitinib and Simvastatin, Chlorpromazine, and most interestingly Hydroxychloroquine (HCQ) which reduces PICALM expression ( Szewczyk-Roszczenko et al, 2023 ).…”

Section: Targeting Cme For Ad Treatmentmentioning

confidence: 99%

“…There have been several clinical trials evaluating endocytosis inhibitors which specifically block CME to treat coronavirus infection ( Szewczyk-Roszczenko et al, 2023 ). These inhibitors include Ruxolitinib and Simvastatin, Chlorpromazine, and most interestingly Hydroxychloroquine (HCQ) which reduces PICALM expression ( Szewczyk-Roszczenko et al, 2023 ). HCQ is a common treatment for arthritis and in 2001 was found to have no significant benefit to early AD ( Van Gool et al, 2001 ).…”

Section: Targeting Cme For Ad Treatmentmentioning

confidence: 99%

Clathrin mediated endocytosis in Alzheimer’s disease: cell type specific involvement in amyloid beta pathology

Jaye,

Sandau,

Saugstad

2024

Front. Aging Neurosci.

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This review provides a comprehensive examination of the role of clathrin-mediated endocytosis (CME) in Alzheimer’s disease (AD) pathogenesis, emphasizing its impact across various cellular contexts beyond neuronal dysfunction. In neurons, dysregulated CME contributes to synaptic dysfunction, amyloid beta (Aβ) processing, and Tau pathology, highlighting its involvement in early AD pathogenesis. Furthermore, CME alterations extend to non-neuronal cell types, including astrocytes and microglia, which play crucial roles in Aβ clearance and neuroinflammation. Dysregulated CME in these cells underscores its broader implications in AD pathophysiology. Despite significant progress, further research is needed to elucidate the precise mechanisms underlying CME dysregulation in AD and its therapeutic implications. Overall, understanding the complex interplay between CME and AD across diverse cell types holds promise for identifying novel therapeutic targets and interventions.

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The Chemical Inhibitors of Endocytosis: From Mechanisms to Potential Clinical Applications

Cited by 19 publications

References 245 publications

Superior performance of biocomposite nanoparticles PLGA-RES in protecting oocytes against vitrification stimuli

Superior performance of biocomposite nanoparticles PLGA-RES in protecting oocytes against vitrification stimuli

Chronic HIV‐1 Tat action induces HLA‐DR downregulation in B cells: A mechanism for lymphoma immune escape in people living with HIV

Clathrin mediated endocytosis in Alzheimer’s disease: cell type specific involvement in amyloid beta pathology

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