Скачать или смотреть Copper Regulates the Canonical NLRP3 Inflammasome

Ever wondered how copper influences your immune system? This groundbreaking study uncovers how copper depletion disrupts NLRP3 inflammasome activation, offering hope for treating inflammatory diseases. Dive into the fascinating world of biochemistry and immunity!

FAQ:
What are inflammasomes?
Inflammasomes are multiprotein complexes within cells that play a crucial role in the innate immune system. They are responsible for activating inflammatory responses, particularly by triggering the production of cytokines like IL-1β and IL-18, and initiating a form of inflammatory cell death called pyroptosis. The NLRP3 inflammasome is one type of inflammasome that has been linked to various diseases.

What is the role of copper in NLRP3 inflammasome activation?
This research demonstrates that intracellular copper is essential for the activation of the NLRP3 inflammasome. Depleting copper using a drug called tetrathiomolybdate (TTM) effectively blocked NLRP3 activation. This suggests that copper plays a critical, and previously unknown, role in regulating NLRP3 activity.

How does TTM affect the NLRP3 inflammasome?
TTM inhibits NLRP3 by binding to and removing copper from the active site of superoxide dismutase 1 (SOD1), an enzyme that normally helps regulate cellular levels of reactive oxygen species (ROS). By inactivating SOD1, TTM disrupts the intracellular redox balance, leading to an increase in ROS, which ultimately inhibits NLRP3 activation.

Are other inflammasomes affected by copper depletion?
No, the effect of copper depletion appears to be specific to the NLRP3 inflammasome. TTM treatment did not affect the activation of other inflammasomes, including AIM2, NLRC4, and NLRP1, nor did it impact the noncanonical inflammasome pathway.

What is the significance of ASC specks in NLRP3 activation?
ASC (apoptosis-associated speck-like protein containing a CARD) is an adaptor protein that forms large aggregates called specks during NLRP3 inflammasome activation. This speck formation is a crucial step in the process. The research showed that copper depletion prevents the formation of ASC specks, further confirming that copper is required for NLRP3 activation.

Does copper depletion have the same effect on all cell types?
Interestingly, the effect of copper depletion on NLRP3 appears to be cell-type specific. While it effectively inhibited NLRP3 in macrophages, it had no effect on monocytes (another type of immune cell) from both mice and humans. This suggests that the redox regulation of NLRP3 might differ between different immune cell types.

What are the potential therapeutic implications of this research?
TTM is already a clinically approved drug for treating copper metabolism disorders. This research suggests that it could potentially be repurposed as an anti-inflammatory treatment for NLRP3-related diseases. By inhibiting NLRP3, TTM could help alleviate inflammation associated with conditions like autoinflammatory syndromes, chronic inflammatory diseases, and even diseases not traditionally considered inflammatory, such as Alzheimer's disease and atherosclerosis.

Does copper chelation affect other inflammatory pathways?
Importantly, TTM treatment did not affect the activation of the NF-κB pathway or the production of other pro-inflammatory cytokines that are typically released through classical secretion mechanisms. This suggests that copper chelation specifically targets the NLRP3 inflammasome without broadly suppressing the immune system.

Video title:
'Copper Regulates the Canonical NLRP3 Inflammasome'

📖 Resources:
Read the research paper 'Copper Regulates the Canonical NLRP3 Inflammasome' written by Nikolaus Deigendesch, Arturo Zychlinsky and Felix Meissner: [https://www.researchgate.net/publicat...]

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