NLRP3 inflammasome: A new target in major depressive disorder

Letter to the Editor.Peer Reviewe

Is Inflammation a Mitochondrial Dysfunction-Dependent Event in Fibromyalgia?

Fibromyalgia (FM) is a complex disorder that affects up to 5% of the general population worldwide. Both mitochondrial dysfunction and inflammation have been implicated in the pathophysiology of FM. We have investigated the possible relationship between mitochondrial dysfunction, oxidative stress, and inflammation in FM. We studied 30 women diagnosed with FM and 20 healthy women. Blood mononuclear cells (BMCs) from FM patients showed reduced level of coenzyme Q10 (CoQ10) and mtDNA contents and high level of mitochondrial reactive oxygen species (ROS) and serum tumor necrosis factor (TNF)-alpha and transcript levels. A significant negative correlation between CoQ10 and TNF-alpha levels (r= -0.588; p < 0.01), and a positive correlation between ROS and TNF-alpha levels (r = 0.791; p < 0.001) were observed accompanied by a significant correlation of visual analogical scale with serum TNF-alpha and transcript levels (r = 0.4507; p < 0.05 and r = 0.7089; p < 0.001, respectively). TNF-alpha release was observed in an in vitro (BMCs) and in vivo (mice) CoQ10 deficiency model. Oral CoQ10 supplementation restored biochemical parameters and induced a significant improvement in clinical symptoms ( p < 0.001). These results lead to the hypothesis that inflammation could be a mitochondrial dysfunction-dependent event implicated in the pathophysiology of FM in several patients indicating at mitochondria as a possible new therapeutic target.Unión Europea FIS PI10/00543Servicio Andaluz de Salud Junta de Andalucía SAS 111242Junta de Andalucía CTS-572

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

AGB Sodium Abundances in the Globular Cluster 47 Tucanae (NGC 104)

A recent analysis comparing the [Na/Fe] distributions of red giant branch (RGB) and asymptotic giant branch (AGB) stars in the Galactic globular cluster NGC 6752 found that the ratio of Na-poor to Na-rich stars changes from 30:70 on the RGB to 100:0 on the AGB. The surprising paucity of Na-rich stars on the AGB in NGC 6752 warrants additional investigations to determine if the failure of a significant fraction of stars to ascend the AGB is an attribute common to all globular clusters. Therefore, we present radial velocities, [Fe/H], and [Na/Fe] abundances for 35 AGB stars in the Galactic globular cluster 47 Tucanae (47 Tuc; NGC 104), and compare the AGB [Na/Fe] distribution with a similar RGB sample published previously. The abundances and velocities were derived from high resolution spectra obtained with the Michigan/Magellan Fiber System (M2FS) and MSpec spectrograph on the Magellan-Clay 6.5m telescope. We find the average heliocentric radial velocity and [Fe/H] values to be =-18.56 km s^-1 (sigma=10.21 km s^-1) and =-0.68 (sigma=0.08), respectively, in agreement with previous literature estimates. The average [Na/Fe] abundance is 0.12 dex lower in the 47 Tuc AGB sample compared to the RGB sample, and the ratio of Na-poor to Na-rich stars is 63:37 on the AGB and 45:55 on the RGB. However, in contrast to NGC 6752, the two 47 Tuc populations have nearly identical [Na/Fe] dispersion and interquartile range values. The data presented here suggest that only a small fraction <20% of Na-rich stars in 47 Tuc may fail to ascend the AGB. Regardless of the cause for the lower average [Na/Fe] abundance in AGB stars, we find that Na-poor stars and at least some Na-rich stars in 47 Tuc evolve through the early AGB phase. [abridged]Comment: Accepted for publication in the Astronomical Journal; 15 pages; 8 figures; 4 table

Mitochondrial dysfunction promoted by Porphyromonas gingivalis lipopolysaccharide as a possible link between cardiovascular disease and periodontitis

Oxidative stress is one of the factors that could explain the pathophysiological mechanism of inflammatory conditions that occur in cardiovascular disease (CVD) and periodontitis. Such inflammatory response is often evoked by specific bacteria, as the lipopolysaccharide (LPS) of Porphyromonas gingivalis is a key factor in this process. The aim of this research was to study the role of mitochondrial dysfunction in peripheral blood mononuclear cells (PBMCs) from periodontitis patients and to evaluate the influence of LPS on fibroblasts to better understand the pathophysiology of periodontitis and its relationship with CVD. PBMCs from patients showed lower CoQ10 levels and citrate synthase activity, together with high levels of ROS production. LPS-treated fibroblasts provoked increased oxidative stress and mitochondrial dysfunction by a decrease in mitochondrial protein expression, mitochondrial mass, and mitochondrial membrane potential. Our study supports the hypothesis that LPS-mediated mitochondrial dysfunction could be at the origin of oxidative stress in periodontal patients. Abnormal PBMC performance may promote oxidative stress and alter cytokine homeostasis. In conclusion, mitochondrial dysfunction could represent a possible link to understanding the interrelationships between two prominent inflammatory diseases: periodontitis and CVD

Inhibition of the NLRP3 inflammasome improves lifespan in animal murine model of Hutchinson-Gilford Progeria

Inflammation is a hallmark of aging and accelerated aging syndromes such as Hutchinson-Gilford progeria syndrome (HGPS). In this study, we present evidence of increased expression of the components of the NLRP3 inflammasome pathway in HGPS skin fibroblasts, an outcome that was associated with morphological changes of the nuclei of the cells. Lymphoblasts from HGPS patients also showed increased basal levels of NLRP3 and caspase 1. Consistent with these results, the expression of caspase 1 and Nlrp3, but not of the other inflammasome receptors was higher in the heart and liver of Zmpste2