Ubiquitination is a major modulator for the activation of inflammasomes and pyroptosis

Jiang, Qiuyun; Zhu, Zhigang; Mao, Xinliang

doi:10.1016/j.bbagrm.2023.194955

Cited by 7 publications

(3 citation statements)

References 120 publications

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“… 291 – 293 The process consists of multiple enzyme-catalyzed stages, involving the coordinated activity of ubiquitin-activating enzymes (E1s) and ubiquitin-conjugating enzymes (E2s) to ubiquitin ligases (E3s), leading to the covalent attachment of ubiquitin to the target protein. 294 – 296 …”

Section: Regulation Of Gasderminsmentioning

confidence: 99%

The gasdermin family: emerging therapeutic targets in diseases

Zhu,

Xu,

Jiang

et al. 2024

Sig Transduct Target Ther

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The gasdermin (GSDM) family has garnered significant attention for its pivotal role in immunity and disease as a key player in pyroptosis. This recently characterized class of pore-forming effector proteins is pivotal in orchestrating processes such as membrane permeabilization, pyroptosis, and the follow-up inflammatory response, which are crucial self-defense mechanisms against irritants and infections. GSDMs have been implicated in a range of diseases including, but not limited to, sepsis, viral infections, and cancer, either through involvement in pyroptosis or independently of this process. The regulation of GSDM-mediated pyroptosis is gaining recognition as a promising therapeutic strategy for the treatment of various diseases. Current strategies for inhibiting GSDMD primarily involve binding to GSDMD, blocking GSDMD cleavage or inhibiting GSDMD-N-terminal (NT) oligomerization, albeit with some off-target effects. In this review, we delve into the cutting-edge understanding of the interplay between GSDMs and pyroptosis, elucidate the activation mechanisms of GSDMs, explore their associations with a range of diseases, and discuss recent advancements and potential strategies for developing GSDMD inhibitors.

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Section: Regulation Of Gasderminsmentioning

confidence: 99%

The gasdermin family: emerging therapeutic targets in diseases

Zhu,

Xu,

Jiang

et al. 2024

Sig Transduct Target Ther

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“…Pattern recognition receptors, such as Toll-like receptors, engage with pathogen-related molecular patterns or damage-related molecular patterns ( Swanson et al, 2019 ), leading to the activation of NLR family pyrin domain containing protein 3 (NLRP3) and nuclear factor kappa-B (NF-κB). Upon NLRP3 activation, apoptosis-associated speck-like protein containing a CARD (ASC) and the precursor of pro-caspase-1 are recruited to form an inflammasome complex ( Jiang et al, 2023b ), subsequently triggering the self-cleavage of pro-caspase-1 to form active caspase-1 ( Meng et al, 2023b ). Besides activation through pattern recognition receptors, NF-κB is also regulated by pro-inflammatory cytokines such as tumor necrosis factor (TNF)-α and interleukin-1β (IL-1β) ( Yu et al, 2020 ), leading to the transcription of inactive pro-IL-18 and pro-IL-1β ( Wang et al, 2023b ).…”

Section: Pharmacological Effects Of Saponin Compoundsmentioning

confidence: 99%

Saponin components in Polygala tenuifolia as potential candidate drugs for treating dementia

Li,

Hou,

et al. 2024

Front. Pharmacol.

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ObjectiveThis study aims to elucidate the intervention effects of saponin components from Polygala tenuifolia Willd (Polygalaceae) on dementia, providing experimental evidence and new insights for the research and application of saponins in the field of dementia.Materials and MethodsThis review is based on a search of the PubMed, NCBI, and Google Scholar databases from their inception to 13 May 2024, using terms such as “P. tenuifolia,” “P. tenuifolia and saponins,” “toxicity,” “dementia,” “Alzheimer’s disease,” “Parkinson’s disease dementia,” and “vascular dementia.” The article summarizes the saponin components of P. tenuifolia, including tenuigenin, tenuifolin, polygalasaponins XXXII, and onjisaponin B, as well as the pathophysiological mechanisms of dementia. Importantly, it highlights the potential mechanisms by which the active components of P. tenuifolia prevent and treat diseases and relevant clinical studies.ResultsThe saponin components of P. tenuifolia can reduce β-amyloid accumulation, exhibit antioxidant effects, regulate neurotransmitters, improve synaptic function, possess anti-inflammatory properties, inhibit neuronal apoptosis, and modulate autophagy. Therefore, P. tenuifolia may play a role in the prevention and treatment of dementia.ConclusionThe saponin components of P. tenuifolia have shown certain therapeutic effects on dementia. They can prevent and treat dementia through various mechanisms.

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“…The inflammasome is a multimeric protein complex essential for the proteolytic activation of IL-1β [ 21 ]. It is extensively regulated through ubiquitination [ 37 ]. IL1B is among the immune response genes activated during the early detection of viral infection ( Figure 1 ).…”

Section: Initiation Of Immune Responsesmentioning

confidence: 99%

Pellino Proteins in Viral Immunity and Pathogenesis

Jensen

2023

Viruses

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Pellino proteins are a family of evolutionarily conserved ubiquitin ligases involved in intracellular signaling in a wide range of cell types. They are essential for microbe detection and the initiation of innate and adaptive immune responses. Some viruses specifically target the Pellino proteins as part of their immune evasion strategies. Through studies of mouse models of viral infections in the central nervous system, heart, lungs, and skin, the Pellino proteins have been linked to both beneficial and detrimental immune responses. Only in recent years have some of the involved mechanisms been identified. The objective of this review is to highlight the many diverse aspects of viral immunity and pathogenesis that the Pellino proteins have been associated with, in order to promote further research into their functions. After a brief introduction to the cellular signaling mechanisms involving Pellino proteins, their physiological roles in the initiation of immune responses, pathogenesis through excess inflammation, immune regulation, and cell death are presented. Known viral immune evasion strategies are also described. Throughout, areas that require more in-depth investigation are identified. Future research into the functions of the Pellino protein family may reveal fundamental insights into how our immune system works. Such knowledge may be leveraged in the fight against viral infections and their sequala.

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Ubiquitination is a major modulator for the activation of inflammasomes and pyroptosis

Cited by 7 publications

References 120 publications

The gasdermin family: emerging therapeutic targets in diseases

The gasdermin family: emerging therapeutic targets in diseases

Saponin components in Polygala tenuifolia as potential candidate drugs for treating dementia

Pellino Proteins in Viral Immunity and Pathogenesis

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