Biological complexity: what capsases do (Introduction)

by David Turell , Thursday, April 16, 2020, 05:45 (1464 days ago) @ dhw

Poorly understood enzyme now gives up it secrets:

https://medicalxpress.com/news/2020-04-secrets-enigmatic-caspase-.html

"The findings show that caspase-6 is a key regulator of innate immunity, inflammasome activation and host defense. Modulation of caspase-6 could be beneficial for treating viral diseases like influenza and other inflammatory diseases including cancer.

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"Caspases are a family of enzymes that regulate programmed cell death (how a cell self-destructs), inflammation and other biological functions. Caspase-6 has previously been characterized as an executioner caspase in a non-inflammatory form of cell death called apoptosis. Caspase-6 has also been linked to neurological disorders like Alzheimer's disease and Huntington disease. However, the full range of the enzyme's function was not well understood. Now, researchers have discovered for the first time how caspase-6 regulates the ZBP1-NLRP3 inflammasome.

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"'Caspase-6 has essential functions in innate immunity, inflammation and in driving PANoptosis."

"The Kanneganti laboratory previously was first to identify ZNA-binding protein 1 (ZBP1) as an innate immune sensor of influenza, an RNA virus. Their work also revealed that ZBP1 triggers inflammatory cell death in the form of pyroptosis, apoptosis and necroptosis, which together are known as PANoptosis.

"PANoptosis is an inflammatory death pathway regulated by components of a structure termed the PANoptosome, which mediates cell death that cannot be assigned to any of the single cell death pathways described previously. In this study, the scientists found that caspase-6 played a critical role in this process.

"The researchers found that caspase-6 interacts with RIPK3 to facilitate the recruitment of RIPK3 to the ZBP1-PANoptosome. This makes caspase-6 crucial for assembly of this ZBP1-mediated inflammatory cell death-inducing complex. In line with these findings, the researchers demonstrated that caspase-6 is required for ZBP1-mediated PANoptosis during viral infection.

"'Caspase-6 deficiency in mice leads to increased susceptibility to influenza virus infection and higher levels of viral replication in the lungs," said first author Min Zheng, Ph.D., of the St. Jude Department of Immunology. "It is likely that the caspase-6-mediated inflammatory cell death pathway is essential to fighting other viruses that activate similar innate immunepathways, potentially including other respiratory viruses.'"

Comment: Another very complex set of actions by a giant enzyme molecule that helps kill cells that need to be removed, an also fights virus infections. A strange mix of activities. An oher example of a system that is so complex, it must be designed.