The Therapeutic Potential of Modifying Inflammasomes and NOD-Like Receptors

Inflammasomes are the central processing units (CPUs) responsible for decoding and integrating signals of foreignness, damage, danger, and distress released by pathogens, cells, and tissues. It was initially thought that the inflammasomes participated only in pathogen recognition and in the pathogen...

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Bibliographic Details
Published inPharmacological reviews Vol. 65; no. 3; pp. 872 - 905
Main Author Di Virgilio, Francesco
Format Journal Article
LanguageEnglish
Published Netherlands Elsevier Inc 01.07.2013
Subjects
Animals
Anti-Inflammatory Agents - therapeutic use
Autophagy
Humans
Inflammasomes - drug effects
Inflammasomes - metabolism
Inflammation - drug therapy
Inflammation - immunology
Inflammation - metabolism
Inflammation Mediators - metabolism
Mitophagy - drug effects
Receptors, Pattern Recognition - drug effects
Receptors, Pattern Recognition - metabolism
Signal Transduction - drug effects
CIITA
VX-765
TP-1
LT
CPU
HMGB1
LRR
TNF
STAND
CARD
ds
FCAS
Aβ
NF-κB
PRR
TBK1
TNL
MAMP
Th
GM-CSF
NACHT
MDP
IFN I
NB-LRR
NOD
IL
MAPK
G-CSF
IPAF
POP
AIM2
PKR
PGN
NOMID
ROS
TXNIP
IAPP
NK
CPPD
NAIP
CNL
NO
T2DM
IL-1Ra
Ag
TTSS
TXN
TANK
LPS
P2X7R
panx
IFN
ASC
CINCA
NLR
miRNA
RLR
PYD
FMF
CC
FIIND
ss
CD
casp-1
VEGF
BIR
ICE
HIN
MSU
MHC I
PAMP
RIG
MAVS
ΑΜD
HET-E
TIR
CAPS
TLRs
DAMP
DC
RIP2
Online AccessGet full text
ISSN0031-6997
1521-0081
1521-0081
DOI10.1124/pr.112.006171

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Abstract Inflammasomes are the central processing units (CPUs) responsible for decoding and integrating signals of foreignness, damage, danger, and distress released by pathogens, cells, and tissues. It was initially thought that the inflammasomes participated only in pathogen recognition and in the pathogenesis of a few, rare, hereditary inflammatory disorders. On the contrary, it is now clear that they have a central role in the pathogenesis of basically all types of chronic inflammation, in metabolic diseases and cancer. So far, six or possibly eight inflammasome subtypes have been identified. Their main, but by no means exclusive, function is to catalyze conversion of pro-IL-1β and pro-IL-18 into their respective mature forms. However, the different inflammasome subtypes may also participate in additional responses, e.g., proliferation, regulation of glycolytic metabolism, or cell activation, albeit it is not clear whether these effects are still mediated through IL-1β release or via modulation of other caspase-1-dependent or -independent pathways. Central to inflammasome organization and activity are proteins belonging to the nucleotide binding domain, leucine-rich repeat, or NOD-like receptor family. One relevant exception is the AIM2 inflammasome. NOD-like receptors belong to the superfamily of pattern recognition receptors, a group of highly conserved molecules specialized in the recognition of invariant molecular patterns diffused across species. Given their potent proinflammatory activity, it is anticipated that inflammasome activation is tightly controlled. In this review, I will summarize essential features of the known NOD-like receptors, the basic molecular structure of inflammasomes, their participation in pathophysiological responses, and their possible exploitation for therapy.
AbstractList Inflammasomes are the central processing units (CPUs) responsible for decoding and integrating signals of foreignness, damage, danger, and distress released by pathogens, cells, and tissues. It was initially thought that the inflammasomes participated only in pathogen recognition and in the pathogenesis of a few, rare, hereditary inflammatory disorders. On the contrary, it is now clear that they have a central role in the pathogenesis of basically all types of chronic inflammation, in metabolic diseases and cancer. So far, six or possibly eight inflammasome subtypes have been identified. Their main, but by no means exclusive, function is to catalyze conversion of pro-IL-1β and pro-IL-18 into their respective mature forms. However, the different inflammasome subtypes may also participate in additional responses, e.g., proliferation, regulation of glycolytic metabolism, or cell activation, albeit it is not clear whether these effects are still mediated through IL-1β release or via modulation of other caspase-1-dependent or -independent pathways. Central to inflammasome organization and activity are proteins belonging to the nucleotide binding domain, leucine-rich repeat, or NOD-like receptor family. One relevant exception is the AIM2 inflammasome. NOD-like receptors belong to the superfamily of pattern recognition receptors, a group of highly conserved molecules specialized in the recognition of invariant molecular patterns diffused across species. Given their potent proinflammatory activity, it is anticipated that inflammasome activation is tightly controlled. In this review, I will summarize essential features of the known NOD-like receptors, the basic molecular structure of inflammasomes, their participation in pathophysiological responses, and their possible exploitation for therapy.Inflammasomes are the central processing units (CPUs) responsible for decoding and integrating signals of foreignness, damage, danger, and distress released by pathogens, cells, and tissues. It was initially thought that the inflammasomes participated only in pathogen recognition and in the pathogenesis of a few, rare, hereditary inflammatory disorders. On the contrary, it is now clear that they have a central role in the pathogenesis of basically all types of chronic inflammation, in metabolic diseases and cancer. So far, six or possibly eight inflammasome subtypes have been identified. Their main, but by no means exclusive, function is to catalyze conversion of pro-IL-1β and pro-IL-18 into their respective mature forms. However, the different inflammasome subtypes may also participate in additional responses, e.g., proliferation, regulation of glycolytic metabolism, or cell activation, albeit it is not clear whether these effects are still mediated through IL-1β release or via modulation of other caspase-1-dependent or -independent pathways. Central to inflammasome organization and activity are proteins belonging to the nucleotide binding domain, leucine-rich repeat, or NOD-like receptor family. One relevant exception is the AIM2 inflammasome. NOD-like receptors belong to the superfamily of pattern recognition receptors, a group of highly conserved molecules specialized in the recognition of invariant molecular patterns diffused across species. Given their potent proinflammatory activity, it is anticipated that inflammasome activation is tightly controlled. In this review, I will summarize essential features of the known NOD-like receptors, the basic molecular structure of inflammasomes, their participation in pathophysiological responses, and their possible exploitation for therapy.
Inflammasomes are the central processing units (CPUs) responsible for decoding and integrating signals of foreignness, damage, danger, and distress released by pathogens, cells, and tissues. It was initially thought that the inflammasomes participated only in pathogen recognition and in the pathogenesis of a few, rare, hereditary inflammatory disorders. On the contrary, it is now clear that they have a central role in the pathogenesis of basically all types of chronic inflammation, in metabolic diseases and cancer. So far, six or possibly eight inflammasome subtypes have been identified. Their main, but by no means exclusive, function is to catalyze conversion of pro-IL-1β and pro-IL-18 into their respective mature forms. However, the different inflammasome subtypes may also participate in additional responses, e.g., proliferation, regulation of glycolytic metabolism, or cell activation, albeit it is not clear whether these effects are still mediated through IL-1β release or via modulation of other caspase-1-dependent or -independent pathways. Central to inflammasome organization and activity are proteins belonging to the nucleotide binding domain, leucine-rich repeat, or NOD-like receptor family. One relevant exception is the AIM2 inflammasome. NOD-like receptors belong to the superfamily of pattern recognition receptors, a group of highly conserved molecules specialized in the recognition of invariant molecular patterns diffused across species. Given their potent proinflammatory activity, it is anticipated that inflammasome activation is tightly controlled. In this review, I will summarize essential features of the known NOD-like receptors, the basic molecular structure of inflammasomes, their participation in pathophysiological responses, and their possible exploitation for therapy.
Author Di Virgilio, Francesco
Author_xml – sequence: 1
  givenname: Francesco
  surname: Di Virgilio
  fullname: Di Virgilio, Francesco
  email: fdv@unife.it
  organization: Department of Morphology, Surgery and Experimental Medicine, Section of General Pathology, University of Ferrara, Ferrara, Italy
BackLink https://www.ncbi.nlm.nih.gov/pubmed/23592611$$D View this record in MEDLINE/PubMed
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Snippet Inflammasomes are the central processing units (CPUs) responsible for decoding and integrating signals of foreignness, damage, danger, and distress released by...
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SubjectTerms Animals
Anti-Inflammatory Agents - therapeutic use
Autophagy
Humans
Inflammasomes - drug effects
Inflammasomes - metabolism
Inflammation - drug therapy
Inflammation - immunology
Inflammation - metabolism
Inflammation Mediators - metabolism
Mitophagy - drug effects
Receptors, Pattern Recognition - drug effects
Receptors, Pattern Recognition - metabolism
Signal Transduction - drug effects
Title The Therapeutic Potential of Modifying Inflammasomes and NOD-Like Receptors
URI https://dx.doi.org/10.1124/pr.112.006171
https://www.ncbi.nlm.nih.gov/pubmed/23592611
https://www.proquest.com/docview/1328545896
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