H2020Индивидуална стипендия2019–2021

Inflapoptosis · Gasdermin D is a novel effector in the extrinsic apoptosis pathway

„Хоризонт 2020“ — Действия „Мария Склодовска-Кюри“

Период: 2019-09-01 → 2021-08-31
Финансиране от ЕС: 191 149 €
Участници: 1
Схема: MSCA-IF

Линиите свързват координатора с партньорите.

Накратко на български

Протеинът Gasdermin D и неговата роля при възпалителни заболявания, предизвикани от TNF, се анализират чрез опити с мишки. Разбирането на тези механизми помага за откриването на нови мишени за бъдещи лекарства.

Този кратък обзор е генериран от изкуствен интелект

Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.

Резултати накратко

Gasdermin D is a novel effector in the extrinsic apoptosis pathway

Gasdermin D (GSDMD) is a recently described pore-forming protein that is important for host defence against infection. However, emerging studies also implicate GSDMD in a variety of inflammatory diseases through poorly characterised mechanisms. The aim of this study is to investigate the molecular and cellular mechanisms by which GSDMD promote inflammatory disease, so that better drug candidates can be identified in future. Here, we characterised the molecular mechanisms by which GSDMD promotes tumour necrosis factor(TNF)-driven diseases. We show that caspase-8-dependent GSDMD activation promotes TNF-driven disease in mice. Our study thus uncovers novel drug targets for TNF-driven diseases.

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз

Цел на проекта

Pyroptosis is a highly inflammatory form of cell death that drives host protection against intracellular pathogens. Pyroptosis is initiated by inflammasome-activated inflammatory caspases (e.g., caspase-1/4/5/11), which cleave gasdermin D to trigger plasma membrane pores. In contrast, apoptosis is driven by apoptotic caspases (e.g. caspase-3/7/8/9), and is traditionally classified as an immunologically silent form of cell death that is important for development and maintenance of homeostasis. However, emerging studies suggest that caspase-8 activation during extrinsic apoptosis promotes inflammation by triggering the assembly of a proinflammatory, multi-protein complex called the NLRP3 inflammasome, through an ill-defined mechanism. A recent study identified a caspase-3 cleavage site within gasdermin D; cleavage of gasdermin D by apoptotic caspase-3 suppresses the cytotoxic function of this protein. These suggest a complex crosstalk between the pyroptosis and apoptosis. Therefore, the aim of this project is to investigate 1) novel proinflammatory functions of gasdermin D during extrinsic apoptosis; 2) the role of gasdermin D in caspase-8-dependent NLRP3 activation; and 3) the importance of caspase-3-mediated gasdermin D inactivation at steady state in vivo and during chemotherapy. This project will greatly enhance the skills and competence of the experienced researcher through advanced training and international mobility, and is in line with Horizon 2020 Work Programme objective.

Оригинален текст от CORDIS (на английски).

Участници

UNIVERSITE DE LAUSANNE · LAUSANNEКоординаторШвейцария