XIAP as a multifaceted molecule in Cellular Signaling

Hanifeh, Mina; Ataei, Farangis

doi:10.1007/s10495-022-01734-z

Cited by 35 publications

(32 citation statements)

References 107 publications

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“…However, IAP also influences other cellular processes, such as the regulation of ubiquitin-dependent NF-κB activation for cell survival ( 112 ). The interaction with the tumor microenvironment and the crosstalk with various cell signaling pathways lead to the complex role of IAP in cancer and immune regulation ( 113 ). The therapeutic results of IAP antagonists need to be further studied.…”

Section: Disruption Of Cd95-mediated Apoptotic Signaling In Gbmsmentioning

confidence: 99%

The dual role of the CD95 and CD95L signaling pathway in glioblastoma

et al. 2022

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Binding of CD95, a cell surface death receptor, to its homologous ligand CD95L, transduces a cascade of downstream signals leading to apoptosis crucial for immune homeostasis and immune surveillance. Although CD95 and CD95L binding classically induces programmed cell death, most tumor cells show resistance to CD95L-induced apoptosis. In some cancers, such as glioblastoma, CD95-CD95L binding can exhibit paradoxical functions that promote tumor growth by inducing inflammation, regulating immune cell homeostasis, and/or promoting cell survival, proliferation, migration, and maintenance of the stemness of cancer cells. In this review, potential mechanisms such as the expression of apoptotic inhibitor proteins, decreased activity of downstream elements, production of nonapoptotic soluble CD95L, and non-apoptotic signals that replace apoptotic signals in cancer cells are summarized. CD95L is also expressed by other types of cells, such as endothelial cells, polymorphonuclear myeloid-derived suppressor cells, cancer-associated fibroblasts, and tumor-associated microglia, and macrophages, which are educated by the tumor microenvironment and can induce apoptosis of tumor-infiltrating lymphocytes, which recognize and kill cancer cells. The dual role of the CD95-CD95L system makes targeted therapy strategies against CD95 or CD95L in glioblastoma difficult and controversial. In this review, we also discuss the current status and perspective of clinical trials on glioblastoma based on the CD95-CD95L signaling pathway.

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Section: Disruption Of Cd95-mediated Apoptotic Signaling In Gbmsmentioning

confidence: 99%

The dual role of the CD95 and CD95L signaling pathway in glioblastoma

et al. 2022

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“…The overexpression of XIAP could protect CA1 hippocampal neurons and retinal ganglion cells from apoptosis in rat brain ischemia model and optic nerve axotomy model [52]. XIAP has been proposed as a therapeutic target for apoptosis-related diseases [53]. In addition to inhibiting apoptosis, XIAP was also involved in regulating inflammation, autophagy, ROS, and copper homeostasis, etc [53].…”

Section: Menscs Secreted Multiple Molecules Playing Neuroregulatory R...mentioning

confidence: 99%

“…XIAP has been proposed as a therapeutic target for apoptosis-related diseases [53]. In addition to inhibiting apoptosis, XIAP was also involved in regulating inflammation, autophagy, ROS, and copper homeostasis, etc [53]. Given that the powerful immunological and/or apoptosis-related regulatory functions of these factors, further research is needed to target these factors to engineer MenSCs for more prominent therapeutic effects.…”

Section: Menscs Secreted Multiple Molecules Playing Neuroregulatory R...mentioning

confidence: 99%

Menstrual blood derived endometrial stem cells alleviate neuroinflammation by modulating microglia polarization in cells and rats Parkinson’s disease models

Wei

Zhang

et al. 2022

Preprint

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Background: The hyperactivation of microglia is closely related to the development of Parkinson's disease (PD). Because of the extensive sources, non-invasive and periodical collection method, human menstrual blood-derived endometrium stem cells (MenSCs) have been explored as a promising tool for treatment of PD. This study aimed to investigate if MenSCs could inhibit neuroinflammation in PD rats by regulating M1/M2 polarization and to excavate the underlying mechanisms. Methods: MenSCs was co-cultured with 6-OHDA-exposed microglia cell lines. Then the morphology of microglia cells and the level of inflammatory factors were assessed by immunofluorescence and qRT-PCR. After MenSCs was transplanted into the brain of PD rats, animal motor function, the expression of tyrosine hydroxylase (TH), and the level of inflammatory factors in the cerebrospinal fluid (CSF) and serum were detected to evaluate the therapeutic potential of MenSCs. Meanwhile, the expression of M1/M2 phenotype related genes was detected by qRTPCR. One protein array kit containing 1000 kinds of factors was used to detect the protein components in the conditioned medium of MenSCs. Finally, bioinformatic analysis was performed to analyze the function of factors secreted by MenSCs and the signal pathways involved in. Results: MenSCs could suppress 6-OHDA-induced microglia cell activation and significantly decrease inflammation in vitro. After transplantation into the brain of PD rats, MenSCs improved animal motor function, which was indicated by the increased movement distance, ambulatory episodes, exercise time on the rotarod, and less contralateral rotation. Additionally, MenSCs reduced the loss of dopaminergic neurons and down-regulated the level of pro-inflammatory factors in the CSF and serum. Moreover, MenSCs significantly down-regulated the expression of M1 microglia markers and meanwhile up-regulated the expression of M2 microglia markers. 176 biological processes including inflammatory response, negative regulation of apoptotic process, and microglial cell activation were enriched by GO-BP analysis. 58 signal pathways including PI3K/Akt and MAPK were enriched by KEGG analysis. Conclusions: In conclusion, our results provide preliminary evidence for the anti-inflammation capacity of MenSCs by regulating microglia polarization. We firstly demonstrated the biological process of factors secreted by MenSCs and the signal pathways involved in using protein array and bioinformatic analysis.

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“…Among the different PCDs [17], apoptosis was the first to be identified in the damaged spinal cord where it is considered a key feature of secondary damage [9]. Apoptotic cell death is controlled by the activation of the caspase cascade, cysteine-aspartyl proteases that are the last effectors of apoptosis and are activated in response to cell death stimuli (see review by Hanifeh and Farangis [18] and references therein). Molecular and biochemical data have shown that the caspase inhibitors from the apoptosis protein family (IAPs) regulate the apoptotic cell death program [19][20][21][22].…”

Section: Billion Dollars In the Unitedmentioning

confidence: 99%

“…Among the members of this family, the X-linked inhibitor of apoptosis protein (XIAP) is the most potent and the most thoroughly characterized [23,24]. XIAP can directly bind and inhibit CASP3, 7, and 9, and also degrade CASP3 and 7 and other proteins that regulate apoptosis like Smac [18]. In addition to apoptosis, XIAP also controls other cellular processes associated with trauma in the CNS such as autophagy [25], necroptosis [26], intracellular ROS production [27], or ER stress [28].…”

Section: Billion Dollars In the Unitedmentioning

confidence: 99%

Overexpression of the X-linked Inhibitor of Apoptosis Protein (XIAP) in Neurons Improves Cell Survival and the Functional Outcome after Traumatic Spinal Cord Injury

Reigada¹,

Maza²,

Muñoz‐Galdeano³

et al. 2022

Preprint

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Trauma to the spinal cord causes extensive neuronal death contributing to the loss of sensory-motor and autonomic functions below the injury level. Apoptosis affects neurons after spinal cord injury (SCI) and is associated with increased caspase activity. Cleavage of X-linked inhibitor of apoptosis protein (XIAP) after SCI may contribute to this rise of caspase activity. Accordingly, we have shown that the elevation of XIAP resulted in increased neuronal survival after SCI and improved functional recovery. Therefore, we hypothesize that neuronal overexpression of XIAP can be neuroprotective after SCI with improved functional recovery. In line with this, studies of a transgenic mouse with overexpression of XIAP in neurons revealed that higher levels of XIAP after spinal cord trauma favours neuronal survival, tissue preservation, and motor recovery after the spinal cord trauma. Using the human SH-SY5Y cells overexpressing XIAP we show further that XIAP reduced caspase activity and apoptotic cell death after pro-apoptotic stimuli. In conclusion, this study shows that the levels of XIAP expression are an important factor for the outcome after spinal cord trauma and identifies XIAP as an important therapeutic target for alleviating the deleterious effects of SCI.

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XIAP as a multifaceted molecule in Cellular Signaling

Cited by 35 publications

References 107 publications

The dual role of the CD95 and CD95L signaling pathway in glioblastoma

The dual role of the CD95 and CD95L signaling pathway in glioblastoma

Menstrual blood derived endometrial stem cells alleviate neuroinflammation by modulating microglia polarization in cells and rats Parkinson’s disease models

Overexpression of the X-linked Inhibitor of Apoptosis Protein (XIAP) in Neurons Improves Cell Survival and the Functional Outcome after Traumatic Spinal Cord Injury

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