Inflammasome and Oral Diseases.

One of the main steps in the development of the life in the earth is multicellularity. It enables cell differentiation and the development of morphological structures within an organism and is an essential factor in how to recognize friendly cells that are part of the multicellular organism and which foreign organisms can be harmful. Recognition includes devices such as the major histocompatibility complex (MHC), and the pattern recognition receptors (PRRs). PRRs are a group of proteins expressed by cells of the innate immune system that identify two classes of products: pathogen-associated molecular patterns (PAMPs), related to microbial pathogens, and damage-associated molecular patterns (DAMPs), associated with cell components that are released during cell damage or death. All these activate the inflammasome, which is a multiprotein oligomer that includes caspase 1, PYCARD, NALP, and caspase 5 (also known as caspase 11 or ICH-3). It is responsible for activation of inflammatory processes and has been shown to induce cell pyroptosis, a programmed cell death distinct from apoptosis, and promotes the maturation of the inflammatory cytokines interleukin 1ß (IL-1ß) and interleukin 18 (IL-18). We review whether inflammasome is related to diseases that can occur in the oral cavity. The mouth is always a possible environment for the development of pathological conditions because of the wide variety of microorganisms. Small variations in the equilibrium of the oral flora can cause disorders that could affect the organism in a systemic form. We provide data on periodontal disease, candidiasis, herpes virus, oral cancer, caries, and other oral diseases. There are very few papers that study this issue; therefore, we need more investigation and publications about inflammatory molecular processes, and more specifically, related to the inflammasome complex.

Cardiovascular diseases, NLRP3 inflammasome, and western dietary patterns.

Cardiovascular diseases (CVD) are the leading cause of death worldwide, with high prevalence in industrialized countries. Cardiovascular risk factors are mainly influenced by diet, which like other lifestyle factors can be modified to either reduce or increase cardiovascular risk. Other metabolic diseases such as metabolic syndrome, type II diabetes mellitus, and obesity are associated to CVD and highly influenced by the diet. Inflammation has demonstrated to be a key factor in the biological progress of these diseases. Interestingly, IL-1ß which is associated to several steps in the development of atherosclerosis, heart disease, and the association of obesity and type II diabetes with CVD, is activated by the inflammasome complex, a multiprotein complex composed of an intracellular sensor, typically a Nod-like receptor (NLR), the precursor procaspase-1, and the adaptor ASC (apoptosis-associated speck-like protein containing a CARD. In the last years, inflammasome complex has been studied in depth and has been associated with the effect of unhealthy diets both from a clinical and experimental view point. We have reviewed the evidences supporting the role of the inflammasome complex in the development of cardiovascular pathology by unhealthy diets and the therapeutic perspectives.

NLRP3-inflammasome inhibition prevents high fat and high sugar diets-induced heart damage through autophagy induction.

The NLRP3-inflammasome complex has emerged as an important component of inflammatory processes in metabolic dysfunction induced by high-caloric diets. In this study, we investigate the molecular mechanisms by which NLRP3 inhibition may attenuate diet-induced cardiac injury. Here we show the cardiac damage induced by high sugar diet (HSD), high fat diet (HFD) or high sugar/fat diet (HSFD) over 15 weeks. Genetic ablation of NLRP3 protected against this damage by autophagy induction and apoptotic control. Furthermore, NLRP3 inhibition by the selective small molecule MCC950 resulted in similar autophagy induction and apoptotic control in hearts after diets. These data were reproduced in THP-1 cells treated with MCC950 and cultured in media supplemented with serum from mice dosed with MCC950 and fed with diets. NLRP3 inhibition exerted beneficial metabolic, and autophagic adaptations in hearts from obesogenic diets. The inhibition of NLRP3 activation may hold promise in the treatment of metabolic and cardiovascular diseases.

Adenosine Monophosphate (AMP)-Activated Protein Kinase: A New Target for Nutraceutical Compounds.

Adenosine monophosphate-activated protein kinase (AMPK) is an important energy sensor which is activated by increases in adenosine monophosphate (AMP)/adenosine triphosphate (ATP) ratio and/or adenosine diphosphate (ADP)/ATP ratio, and increases different metabolic pathways such as fatty acid oxidation, glucose transport and mitochondrial biogenesis. In this sense, AMPK maintains cellular energy homeostasis by induction of catabolism and inhibition of ATP-consuming biosynthetic pathways to preserve ATP levels. Several studies indicate a reduction of AMPK sensitivity to cellular stress during aging and this could impair the downstream signaling and the maintenance of the cellular energy balance and the stress resistance. However, several diseases have been related with an AMPK dysfunction. Alterations in AMPK signaling decrease mitochondrial biogenesis, increase cellular stress and induce inflammation, which are typical events of the aging process and have been associated to several pathological processes. In this sense, in the last few years AMPK has been identified as a very interesting target and different nutraceutical compounds are being studied for an interesting potential effect on AMPK induction. In this review, we will evaluate the interaction of the different nutraceutical compounds to induce the AMPK phosphorylation and the applications in diseases such as cancer, type II diabetes, neurodegenerative diseases or cardiovascular diseases.