Search results for "Teas"

The Alzheimer’s disease associated bacterial protease RgpB from P. gingivalis activates the alternative β-secretase meprin β thereby increasing Aβ ge…

2019

AbstractAlzheimer’s disease (AD) is the most common type of dementia and characterized by tau hyperphosphorylation, oxidative stress, reactive microglia and amyloid-β (Aβ) deposits. A recent study revealed that Porphyromonas gingivalis infection is associated with amyloid β generation in Alzheimer’s disease. Increased Aβ levels, tau degradation and neuronal toxicity were observed as a consequence of ginigipain R (RgpB) activity, a cysteine protease constitutively secreted by P. gingivalis. Of note, we previously identified RgpB as a potent activator of the metalloproteinase meprin β. Interestingly, meprin β is an alternative β-secretase of the amyloid precursor protein (APP), which together…

Functional and structural insights into astacin metallopeptidases

2012

The astacins are a family of multi-domain metallopeptidases with manifold functions in metabolism. They are either secreted or membrane-anchored and are regulated by being synthesized as inactive zymogens and also by colocalizing protein inhibitors. The distinct family members consist of N-terminal signal peptides and pro-segments, zincdependent catalytic domains, further downstream extracellular domains, transmembrane anchors, and cytosolic domains. The catalytic domains of four astacins and the zymogen of one of these have been structurally characterized and shown to comprise compact ~200-residue zinc-dependent moieties divided into an N-terminal and a C-terminal sub-domain by an active-s…

Effect of antiretroviral protease inhibitors alone, and in combination with paromomycin, on the excystation, invasion and in vitro development of Cry…

2003

With the spread of the human immunodeficiency virus in the early 1980s, cryptosporidiosis was regarded as an AIDS-defining disease. As an opportunistic pathogen, the intestinal parasite Cryptosporidium parvum became an important cause of chronic diarrhoea, leading to high morbidity and mortality in immunocompromised patients. To date, no effective chemotherapy is available. With the introduction of protease inhibitors (PIs) in highly active antiretroviral therapy (HAART), the incidence of cryptosporidiosis in AIDS patients has declined substantially in western countries. We have therefore tested the effect of five PIs used in HAART on the excystation, invasion and development of the parasit…

The cultivable human oral gluten-degrading microbiome and its potential implications in coeliac disease and gluten sensitivity

2013

AbstractCoeliac disease is characterized by intestinal inflammation caused by gluten, proteins which are widely contained in the Western diet. Mammalian digestive enzymes are only partly capable of cleaving gluten, and fragments remain that induce toxic responses in patients with coeliac disease. We found that the oral microbiome is a novel and rich source of gluten-degrading organisms. Here we report on the isolation and characterization of the cultivable resident oral microbes that are capable of cleaving gluten, with special emphasis on the immunogenic domains. Bacteria were obtained by a selective culturing approach and enzyme activities were characterized by: (i) hydrolysis of paranitr…

Darunavir en situaciones especiales

2016

Vibrio Proteases for Biomedical Applications: Modulating the Proteolytic Secretome of V. alginolyticus and V. parahaemolyticus for Improved Enzymes P…

2019

Proteolytic enzymes are of great interest for biotechnological purposes, and their large-scale production, as well as the discovery of strains producing new molecules, is a relevant issue. Collagenases are employed for biomedical and pharmaceutical purposes. The high specificity of collagenase-based preparations toward the substrate strongly relies on the enzyme purity. However, the overall activity may depend on the cooperation with other proteases, the presence of which may be essential for the overall enzymatic activity, but potentially harmful for cells and tissues. Vibrios produce some of the most promising bacterial proteases (including collagenases), and their exo-proteome includes s…

Genes, Ageing and Longevity in Humans: Problems, Advantages and Perspectives.

2006

Many epidemiological data indicate the presence of a strong familial component of longevity that is largely determined by genetics, and a number of possible associations between longevity and allelic variants of genes have been described. A breakthrough strategy to get insight into the genetics of longevity is the study of centenarians, the best example of successful ageing. We review the main results regarding nuclear genes as well as the mitochondrial genome, focusing on the investigations performed on Italian centenarians, compared to those from other countries. These studies produced interesting results on many putative "longevity genes". Nevertheless, many discrepancies are reported, l…

Mitochondrial interference by anti-HIV drugs: mechanisms beyond Pol-γ inhibition.

2011

The combined pharmacological approach to the treatment of HIV infection, known as highly active antiretroviral therapy (HAART), has dramatically reduced AIDS-related morbidity and mortality. However, its use has been associated with serious adverse reactions, of which those resulting from mitochondrial dysfunction are particularly widespread. Nucleos(t)ide-reverse transcriptase inhibitors (NRTIs) have long been considered the main source of HAART-related mitochondrial toxicity due to their ability to inhibit Pol-γ, the DNA polymerase responsible for the synthesis of mitochondrial DNA. Nevertheless, accumulating evidence points to a more complex relationship between these organelles and NRTI…

In Silico Insights into the SARS CoV-2 Main Protease Suggest NADH Endogenous Defences in the Control of the Pandemic Coronavirus Infection

2020

COVID-19 is a pandemic health emergency faced by the entire world. The clinical treatment of the severe acute respiratory syndrome (SARS) CoV-2 is currently based on the experimental administration of HIV antiviral drugs, such as lopinavir, ritonavir, and remdesivir (a nucleotide analogue used for Ebola infection). This work proposes a repurposing process using a database containing approximately 8000 known drugs in synergy structure- and ligand-based studies by means of the molecular docking and descriptor-based protocol. The proposed in silico findings identified new potential SARS CoV-2 main protease (MPRO) inhibitors that fit in the catalytic binding site of SARS CoV-2 MPRO. Several sel…

Molecular architecture and activation of the insecticidal protein Vip3Aa from Bacillus thuringiensis

2020

9 p.-5 fig.