NLRP3 inflammasome inhibition by MCC950 in aged mice improves health via enhanced autophagy and PPARα activity.

08:00 EDT 11th October 2019 | BioPortfolio

Summary of "NLRP3 inflammasome inhibition by MCC950 in aged mice improves health via enhanced autophagy and PPARα activity."

The NLRP3 inflammasome has emerged as an important regulator of metabolic disorders and age-associated diseases as reported in NLRP3 deficient mice. Here we asked whether in old mice C57BL6J the NLRP3 inflammasome inhibitor MCC950 is able to attenuate age- assocociated metabolic syndrome providing health benefits. We report that MCC950 attenuates metabolic and hepatic dysfunction in aged mice. MCC950 inhibited the Pi3K/AKT/mTOR pathway, and enhanced autophagy and activated peroxisome proliferator-activated receptor alpha (PPARα) in vivo and in vitro. The data suggest that MCC950 mediates the protective effects by mTOR inhibiton activating autophagy and PPARα. In conclusion, pharmacological inhibition of NLRP3 in aged mice has a significant impact on health. Thus, NLRP3 may be a therapeutic target of human age-associated metabolic syndrome.


Journal Details

This article was published in the following journal.

Name: The journals of gerontology. Series A, Biological sciences and medical sciences
ISSN: 1758-535X


DeepDyve research library

PubMed Articles [26922 Associated PubMed Articles listed on BioPortfolio]

MCC950/CRID3 potently targets the NACHT domain of wild-type NLRP3 but not disease-associated mutants for inflammasome inhibition.

The nucleotide-binding-domain (NBD)-and leucine-rich-repeat (LRR)-containing (NLR) family, pyrin-domain-containing 3 (NLRP3) inflammasome drives pathological inflammation in a suite of autoimmune, met...

NLRP3 inflammasome inhibition attenuates cisplatin-induced renal fibrosis by decreasing oxidative stress and inflammation.

The NOD-like receptor, pyrin domain containing-3 (NLRP3) inflammasome is involved in the progression of chronic kidney disease in several rodent models. Here, we investigated whether a specific inhibi...

Pharmacological inhibition of the NLRP3 inflammasome as a potential target for cancer-induced bone pain.

Cancer-induced bone pain (CIBP) remains a major challenge in patients suffering from bone metastases because of the complex mechanisms and unsatisfactory treatments. Emerging evidence have shown that ...

MCC950 blocks enhanced interleukin-1β production in patients with NLRP3 low penetrance variants.

To determine the role of the NLRP3 inflammasome by using the selective NLRP3 inhibitor MCC950 in patients with NLRP3 low penetrance variants and clinical symptoms suggestive for an autoinflammatory sy...

The microglial NLRP3 inflammasome is activated by amyotrophic lateral sclerosis proteins.

Microglial NLRP3 inflammasome activation is emerging as a key contributor to neuroinflammation during neurodegeneration. Pathogenic protein aggregates such as β-amyloid and α-synuclein trigger micro...

Clinical Trials [9353 Associated Clinical Trials listed on BioPortfolio]

Role of the NLRP3 Inflammasome in Escherichia Coli and Staphylococcus Aureus Bacteria

Our previous studies delineate a novel pathway of immune activation in animals that the investigators have named Anti-Virulence Immunity (AVI). Using a mice model of bacteremia, the invest...

P2X7 Receptor, Inflammation and Neurodegenerative Diseases

Parkinson disease (PD) is a chronic degenerative disease characterized by a progressive loss of dopaminergic neurons in the substantia nigra. Its pathophysiological mechanisms are still pa...

A Proof-of-Concept Study of Topical AC-203 in Patients With Bullous Pemphigoid

Bullous pemphigoid (BP) is a chronic, inflammatory, subepidermal, autoimmune blistering disease which mainly develops in the elderly, with onset usually in the late 70s and a substantial i...

Effect of Fasting on the NLRP3 Inflammasome

Background: - Restricting calories can help a person reduce risk factors for heart disease. Researchers have found that not eating or drinking anything but water for 24 hours prevents the...

Role of Mitochondrial Dysfunction in the Occurrence of Acute Kidney Injury (AKI) in Postoperative Cardiac Surgery

Cardiac Surgery and Acute Kidney Failure (AKI) post Surgery: AKI is a frequent complication in the immediate aftermath of cardiac surgery with an incidence varying from 5 to 40%. KDIGO cr...

Medical and Biotech [MESH] Definitions

Services for the diagnosis and treatment of diseases in the aged and the maintenance of health in the elderly.

An NLR protein that contains an N-terminal PYRIN DOMAIN and ATP-binding site and 9 C-terminal LEUCINE-rich repeats; it is expressed primarily by MACROPHAGES. It is a core component of the INFLAMMASOME and directs its assembly in response to pathogen infection and damage-associated stimuli. Mutations in the NLRP3 gene are associated with FAMILIAL COLD AUTOINFLAMMATORY SYNDROME.

Strains of mice arising from a parental inbred stock that was subsequently used to produce substrains of knockout and other mutant mice with targeted mutations.

Mice homozygous for the mutant autosomal recessive gene "scid" which is located on the centromeric end of chromosome 16. These mice lack mature, functional lymphocytes and are thus highly susceptible to lethal opportunistic infections if not chronically treated with antibiotics. The lack of B- and T-cell immunity resembles severe combined immunodeficiency (SCID) syndrome in human infants. SCID mice are useful as animal models since they are receptive to implantation of a human immune system producing SCID-human (SCID-hu) hematochimeric mice.

A subspecialty of psychiatry concerned with the mental health of the aged.

Quick Search

DeepDyve research library

Relevant Topic

Hepatology is the study of liver, gallbladder, biliary tree, and pancreas, and diseases associated with them. This includes viral hepatitis, alcohol damage, cirrhosis and cancer. As modern lifestyles change, with alcoholism and cancer becoming more promi...

Searches Linking to this Article