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Open AccessJournal ArticleDOI

Caspase Functions in Cell Death and Disease

TLDR
Dysregulation of caspases underlies human diseases including cancer and inflammatory disorders, and major efforts to design better therapies for these diseases seek to understand how these enzymes work and how they can be controlled.
Abstract
Caspases are a family of endoproteases that provide critical links in cell regulatory networks controlling inflammation and cell death. The activation of these enzymes is tightly controlled by their production as inactive zymogens that gain catalytic activity following signaling events promoting their aggregation into dimers or macromolecular complexes. Activation of apoptotic caspases results in inactivation or activation of substrates, and the generation of a cascade of signaling events permitting the controlled demolition of cellular components. Activation of inflammatory caspases results in the production of active proinflammatory cytokines and the promotion of innate immune responses to various internal and external insults. Dysregulation of caspases underlies human diseases including cancer and inflammatory disorders, and major efforts to design better therapies for these diseases seek to understand how these enzymes work and how they can be controlled.

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Journal ArticleDOI

Aggregation-Induced Emission: Together We Shine, United We Soar!

TL;DR: This paper presents a meta-analysis of the chiral stationary phase transition of Na6(CO3)(SO4)2, a major component of the response of the immune system to Na2CO3.
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Inflammatory caspases are innate immune receptors for intracellular LPS

TL;DR: It is shown that human monocytes, epithelial cells and keratinocytes undergo necrosis upon cytoplasmic delivery of LPS, which represents a new mode of pattern recognition in immunity and also an unprecedented means of caspase activation.
Journal ArticleDOI

The molecular machinery of regulated cell death

TL;DR: The in-depth comprehension of each of these lethal subroutines and their intercellular consequences may uncover novel therapeutic targets for the avoidance of pathogenic cell loss.
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Old, new and emerging functions of caspases.

TL;DR: Caspase-2 has emerged as a unique caspase with potential roles in maintaining genomic stability, metabolism, autophagy and aging, and some of these less studied and emerging functions of mammalian caspases are focused on.
Journal ArticleDOI

Targeting apoptosis in cancer therapy

TL;DR: The main pathways that regulate apoptosis as well as other signalling pathways that interact with them are presented, highlighting actionable molecular targets for anticancer therapy and an overview of therapeutic agents exploiting apoptosis currently in clinical translation and known mechanisms of resistance to these agents are provided.
References
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Journal ArticleDOI

The plant immune system

TL;DR: A detailed understanding of plant immune function will underpin crop improvement for food, fibre and biofuels production and provide extraordinary insights into molecular recognition, cell biology and evolution across biological kingdoms.
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A human homologue of the Drosophila Toll protein signals activation of adaptive immunity

TL;DR: The cloning and characterization of a human homologue of the Drosophila toll protein (Toll) is reported, which has been shown to induce the innate immune response in adult Dosophila.
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The inflammasome: a molecular platform triggering activation of inflammatory caspases and processing of proIL-beta.

TL;DR: In this article, the inflammasome is identified as a caspase-activating complex that comprises caspases-1, casp-5, Pycard/Asc, and NALP1, a Pyrin domain-containing protein sharing structural homology with NODs.
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Gout-associated uric acid crystals activate the NALP3 inflammasome

TL;DR: It is shown that MSU and CPPD engage the caspase-1-activating NALP3 (also called cryopyrin) inflammasome, resulting in the production of active interleukin (IL)-1β and IL-18 in mice deficient in the IL-1β receptor.
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Caspase-12 mediates endoplasmic-reticulum-specific apoptosis and cytotoxicity by amyloid-beta.

TL;DR: It is shown that caspase-12 is localized to the ER and activated by ER stress, including disruption of ER calcium homeostasis and accumulation of excess proteins in ER, but not by membrane- or mitochondrial-targeted apoptotic signals, which may contribute to amyloid-β neurotoxicity.
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