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The Role of Non-canonical and Canonical Inflammasomes in Inflammaging

Neurodegenerative diseases currently affect millions of people worldwide and continues to increase in the expanding elderly population. Neurodegenerative diseases usually involve cognitive decline and are among the top causes of death. Thus, there is a critical need for the development of treatments...

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Autores principales: Cyr, Brianna, Hadad, Roey, Keane, Robert W., de Rivero Vaccari, Juan Pablo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8864077/
https://www.ncbi.nlm.nih.gov/pubmed/35221912
http://dx.doi.org/10.3389/fnmol.2022.774014
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author Cyr, Brianna
Hadad, Roey
Keane, Robert W.
de Rivero Vaccari, Juan Pablo
author_facet Cyr, Brianna
Hadad, Roey
Keane, Robert W.
de Rivero Vaccari, Juan Pablo
author_sort Cyr, Brianna
collection PubMed
description Neurodegenerative diseases currently affect millions of people worldwide and continues to increase in the expanding elderly population. Neurodegenerative diseases usually involve cognitive decline and are among the top causes of death. Thus, there is a critical need for the development of treatments and preventive strategies for neurodegenerative diseases. One of the risk factors of neurodegeneration is inflammaging, a low level of chronic inflammation due to old age. We have previously shown that the inflammasome contributes to inflammaging in the central nervous system (CNS). The inflammasome is a multiprotein complex of the innate immune response consisting of a sensor protein, apoptosis speck-like protein containing a CARD (ASC), and caspase-1. Our lab has developed a humanized monoclonal antibody against ASC (anti-ASC). Here, we analyzed cortical lysates from young (3 months old), aged (18 months old), and aged anti-ASC treated mice for the expression of canonical and non-canonical inflammasome proteins. We show that the protein levels of NLRP1, ASC, caspase-1, and caspase-8 were elevated in the cortex of aged mice, and that anti-ASC decreased the expression of these proteins, consistent with lower levels of the pro-inflammatory cytokine interleukin (IL)-1β. Additionally, we show that these proteins form a novel NLRP1-caspase-8 non-canonical inflammasome comprised of NLRP1, caspase-8 and ASC. Moreover, these inflammasome proteins were present in neurons in young and aged mice. Together, these results indicate that a novel NLRP1-caspase-8 non-canonical inflammasome is present in the cortex of mice and that anti-ASC is a potential therapeutic to decrease inflammasome-mediated inflammaging in the CNS.
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spelling pubmed-88640772022-02-24 The Role of Non-canonical and Canonical Inflammasomes in Inflammaging Cyr, Brianna Hadad, Roey Keane, Robert W. de Rivero Vaccari, Juan Pablo Front Mol Neurosci Molecular Neuroscience Neurodegenerative diseases currently affect millions of people worldwide and continues to increase in the expanding elderly population. Neurodegenerative diseases usually involve cognitive decline and are among the top causes of death. Thus, there is a critical need for the development of treatments and preventive strategies for neurodegenerative diseases. One of the risk factors of neurodegeneration is inflammaging, a low level of chronic inflammation due to old age. We have previously shown that the inflammasome contributes to inflammaging in the central nervous system (CNS). The inflammasome is a multiprotein complex of the innate immune response consisting of a sensor protein, apoptosis speck-like protein containing a CARD (ASC), and caspase-1. Our lab has developed a humanized monoclonal antibody against ASC (anti-ASC). Here, we analyzed cortical lysates from young (3 months old), aged (18 months old), and aged anti-ASC treated mice for the expression of canonical and non-canonical inflammasome proteins. We show that the protein levels of NLRP1, ASC, caspase-1, and caspase-8 were elevated in the cortex of aged mice, and that anti-ASC decreased the expression of these proteins, consistent with lower levels of the pro-inflammatory cytokine interleukin (IL)-1β. Additionally, we show that these proteins form a novel NLRP1-caspase-8 non-canonical inflammasome comprised of NLRP1, caspase-8 and ASC. Moreover, these inflammasome proteins were present in neurons in young and aged mice. Together, these results indicate that a novel NLRP1-caspase-8 non-canonical inflammasome is present in the cortex of mice and that anti-ASC is a potential therapeutic to decrease inflammasome-mediated inflammaging in the CNS. Frontiers Media S.A. 2022-02-09 /pmc/articles/PMC8864077/ /pubmed/35221912 http://dx.doi.org/10.3389/fnmol.2022.774014 Text en Copyright © 2022 Cyr, Hadad, Keane and de Rivero Vaccari. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Molecular Neuroscience
Cyr, Brianna
Hadad, Roey
Keane, Robert W.
de Rivero Vaccari, Juan Pablo
The Role of Non-canonical and Canonical Inflammasomes in Inflammaging
title The Role of Non-canonical and Canonical Inflammasomes in Inflammaging
title_full The Role of Non-canonical and Canonical Inflammasomes in Inflammaging
title_fullStr The Role of Non-canonical and Canonical Inflammasomes in Inflammaging
title_full_unstemmed The Role of Non-canonical and Canonical Inflammasomes in Inflammaging
title_short The Role of Non-canonical and Canonical Inflammasomes in Inflammaging
title_sort role of non-canonical and canonical inflammasomes in inflammaging
topic Molecular Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8864077/
https://www.ncbi.nlm.nih.gov/pubmed/35221912
http://dx.doi.org/10.3389/fnmol.2022.774014
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