PMID- 27187378
OWN - NLM
STAT- MEDLINE
DCOM- 20170309
LR  - 20181113
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 17
IP  - 5
DP  - 2016 May 13
TI  - The Relationship between NALP3 and Autoinflammatory Syndromes.
LID - 10.3390/ijms17050725 [doi]
LID - 725
AB  - The nucleotide-binding domain, leucine-rich repeat/pyrin domain-containing-3 
      (NALP3) inflammasome, which is required for synthesis of interleukin-1beta, has been 
      implicated in the pathogenesis of several autoinflammatory syndromes. This review 
      of the literature summarizes the interconnectedness of NALP3 inflammasome with 
      some of these disorders. Familial Mediterranean fever results from a mutation in 
      the Mediterranean fever (MEFV) gene, which encodes the pyrin protein. Previous 
      study results suggest that pyrin suppresses caspase-1 activation, perhaps by 
      competing for the adaptor protein, termed, pyrin domain of apoptosis/speck-like 
      protein containing a caspase-recruitment domain (ACS) which therefore interferes 
      with NALP3 inflammasome activation. The nucleotide-binding domain, leucine-rich 
      repeat/pyrin domain-containing-3 (NALP3) inflammasome is constitutively activated 
      in cryopyrin-associated periodic syndromes due to gain-of-function mutations 
      resulting from point mutations within the neuronal apoptosis inhibitor 
      protein/class 2 transcription factor/heterokaryon 
      incompatibility/telomerase-associated protein-1 (NACHT) domain of the NALP3 
      protein. Pyogenic arthritis, pyoderma gangrenosum and acne (PAPA) syndrome is 
      caused by mutations in the genes encoding proline-serine-threonine phosphatase 
      interacting protein 1 (PSTPIP1). These PSTPIP1 mutants are thought to bind to 
      pyrin causing an increase in the pyrin domain of apoptosis/speck-like protein 
      containing a caspase-recruitment domain (ASC) pyroptosome assembly leading to 
      procaspase-1 recruitment and therefore its activation. Hyperimmunoglublinemia D 
      syndrome is caused by mevalonate kinase (MVK) deficiency, which may be affected 
      by protein accumulation that leads to NALP3 inflammasome activation. Tumor 
      necrosis factor receptor-associated periodic syndrome is associated with 
      mutations in the tumor necrosis factor receptor superfamily, member 1A (TNFRSF1A) 
      gene which decreases the level of soluble tumor necrosis factor receptor-1 
      (TNFR1) leading to neutralization of tumor necrosis factor (TNF)-alpha. In general, 
      these autoinflammatory disorders have shown a clinical response to interleukin-1 
      (IL-1) antagonists, suggesting that the NALP3 inflammasome serves a critical role 
      in their pathogenesis.
FAU - Campbell, Lorna
AU  - Campbell L
AD  - Rheumatology Fellows at University Hospitals Case Medical Center, Cleveland, OH 
      44106-5076, USA. lorna.campbell@uhhospitals.org.
FAU - Raheem, Irfan
AU  - Raheem I
AD  - Rheumatology Fellows at University Hospitals Case Medical Center, Cleveland, OH 
      44106-5076, USA. irfan.raheem@uhhospitals.org.
FAU - Malemud, Charles J
AU  - Malemud CJ
AD  - Department of Medicine, Division of Rheumatic Diseases, Case Western Reserve 
      University School of Medicine and University Hospitals Case Medical Center, 2061 
      Cornell Road, Cleveland, OH 44106-5076, USA. cjm4@cwru.edu.
FAU - Askari, Ali D
AU  - Askari AD
AD  - Department of Medicine, Division of Rheumatic Diseases, Case Western Reserve 
      University School of Medicine and University Hospitals Case Medical Center, 2061 
      Cornell Road, Cleveland, OH 44106-5076, USA. ali.askari@uhhospitals.org.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20160513
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (Immunosuppressive Agents)
RN  - 0 (Inflammasomes)
RN  - 0 (NLR Family, Pyrin Domain-Containing 3 Protein)
RN  - 0 (NLRP3 protein, human)
SB  - IM
MH  - Animals
MH  - Anti-Inflammatory Agents/therapeutic use
MH  - Hereditary Autoinflammatory Diseases/drug therapy/*genetics/immunology
MH  - Humans
MH  - Immunosuppressive Agents/pharmacology/therapeutic use
MH  - Inflammasomes/drug effects/genetics/immunology
MH  - NLR Family, Pyrin Domain-Containing 3 Protein/*genetics/metabolism
PMC - PMC4881547
OTO - NOTNLM
OT  - NALP3 inflammasome
OT  - autoinflammatory syndromes
OT  - interleukin IL-1beta
EDAT- 2016/05/18 06:00
MHDA- 2017/03/10 06:00
PMCR- 2016/05/01
CRDT- 2016/05/18 06:00
PHST- 2016/03/17 00:00 [received]
PHST- 2016/05/06 00:00 [revised]
PHST- 2016/05/06 00:00 [accepted]
PHST- 2016/05/18 06:00 [entrez]
PHST- 2016/05/18 06:00 [pubmed]
PHST- 2017/03/10 06:00 [medline]
PHST- 2016/05/01 00:00 [pmc-release]
AID - ijms17050725 [pii]
AID - ijms-17-00725 [pii]
AID - 10.3390/ijms17050725 [doi]
PST - epublish
SO  - Int J Mol Sci. 2016 May 13;17(5):725. doi: 10.3390/ijms17050725.