AC-YVAD-CMK Inhibits Pyroptosis and Improves Functional Outcome after Intracerebral Hemorrhage.

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  • Additional Information
    • Source:
      Publisher: Wiley Country of Publication: United States NLM ID: 101600173 Publication Model: eCollection Cited Medium: Internet ISSN: 2314-6141 (Electronic) NLM ISO Abbreviation: Biomed Res Int Subsets: MEDLINE
    • Publication Information:
      Publication: 2024- : [Hoboken, NJ] : Wiley
      Original Publication: New York, NY : Hindawi Pub. Co.
    • Subject Terms:
      Amino Acid Chloromethyl Ketones/*pharmacology ; Cerebral Hemorrhage/*metabolism ; Neuroprotective Agents/*pharmacology ; Pyroptosis/*drug effects; Animals ; Behavior, Animal/drug effects ; Caspase 1/metabolism ; Caspase Inhibitors ; Inflammasomes/metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Microglia/drug effects ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism
    • Abstract:
      Intracerebral hemorrhage (ICH) refers to bleeding in the brain and is associated with the release of large amount of inflammasomes, and the activation of different cell death pathways. These cell death pathways lead to removal of inactivated and damaged cells and also result in neuronal cell damage. Pyroptosis is a newly discovered cell death pathway that has gained attention in recent years. This pathway mainly depends on activation of caspase-1-mediated cascades to cause cell death. We tested a well-known selective inhibitor of caspase-1, AC-YVAD-CMK, which has previously been found to have neuroprotective effects in ICH mice model, to ascertain its effects on the activation of inflammasomes mediated pyroptosis. Our results showed that AC-YVAD-CMK could reduce caspase-1 activation and inhibit IL-1 β production and maturation, but has no effect on NLRP3 expression, an upstream inflammatory complex. AC-YVAD-CMK administration also resulted in reduction in M1-type microglia polarization around the hematoma, while increasing the number of M2-type cells. Furthermore, AC-YVAD-CMK treated mice showed some recovery of neurological function after hemorrhage especially at the hyperacute and subacute stage resulting in some degree of limb movement. In conclusion, we are of the view that AC-YVAD-CMK could inhibit pyroptosis, decrease the secretion or activation of inflammatory factors, and affect the polarization of microglia resulting in improvement of neurological function after ICH.
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    • Accession Number:
      0 (Amino Acid Chloromethyl Ketones)
      0 (Caspase Inhibitors)
      0 (Inflammasomes)
      0 (N-acetyl-tyrosyl-valyl-alanyl-aspartyl chloromethyl ketone)
      0 (NLR Family, Pyrin Domain-Containing 3 Protein)
      0 (Neuroprotective Agents)
      EC 3.4.22.36 (Caspase 1)
    • Publication Date:
      Date Created: 20181110 Date Completed: 20190221 Latest Revision: 20190221
    • Publication Date:
      20250114
    • Accession Number:
      PMC6206581
    • Accession Number:
      10.1155/2018/3706047
    • Accession Number:
      30410928