The present invention relates to novel NADPH oxidase proteins, or Nox, the use thereof, the method of preparation thereof and the method for identification thereof.

The serotonin receptor 5HT2A (5HT2aR) and membrane NADPH oxidases (NOX enzymes) are found to be a target of autoantibodies present in Multiple Sclerosis patients. The present invention refers to peptides comprised in the extracellular regions of the human 5HT2aR and/or NOXs for diagnosis and therapy of Multiple Sclerosis.

Polypeptide scaffolds comprising enzymatic proteins are provided. The enzymatic polypeptide scaffolds comprise heterologous enzymes to form a heterologous metabolic pathway, and can be targeted to a substrate through a surface anchoring domain. The enzymatic polypeptide scaffolds leverage the high specificity and affinity protein/protein interaction between the cohesins and dockerins of microorganismal cellulosomes to form custom enzymatic arrays.

A NADPH oxidase (Nox) protein includes a domain including 3 to 7 transmembrane helices, and an amino acid sequence including at least 2 bis-histidyl motifs, wherein each of the bis-histidyl motifs consists of 2 histidine residues separated by 12, 13 or 14 amino acid residues. The Nox protein may be produced by a method that includes solubilizing a solution of cells expressing the Nox protein using a detergent from the maltoside family to suspend the Nox protein in the solution.

The present invention relates to novel peptides, compositions and methods for the prevention and/or treatment of pathological conditions and diseases associated with NADPH oxidase 1 (Nox1) activity, and/or increased reactive oxygen species (ROS) production. The novel peptides are thus particularly useful for treating and/or preventing cancer, atherosclerosis, angiogenesis, and aging.

The present disclosure is related to genetically engineered microbial strains and related bioprocesses for the production of pyruvate and related products. Specifically, the use of dynamically controlled synthetic metabolic valves to reduce the activity of enzymes known to contribute to pyruvate synthesis, leads to increased pyruvate production in a two-stage process rather than a decrease in production.

The present invention relates to compositions comprising a polymeric matrix or a gel containing functional enzymes capable of re-creating under culture conditions the cell microenvironment existing in vivo. The present invention also relates to devices for cell cultures comprising such compositions, in particular hydrogel and the use thereof to control the chemical microenvironment of a cell culture or mimic physiological or pathological conditions of the in vivo cells. The compositions and the devices described herein could be also used in vitro for evaluating the therapeutic effect of a compound on a determined cell line or on primary cells.

The present invention relates to compositions comprising a polymeric matrix or a gel containing functional enzymes capable of re-creating under culture conditions the cell microenvironment existing in vivo. The present invention also relates to devices for cell cultures comprising such compositions, in particular hydrogel and the use thereof to control the chemical microenvironment of a cell culture or mimic physiological or pathological conditions of the in vivo cells. The compositions and the devices described herein could be also used in vitro for evaluating the therapeutic effect of a compound on a determined cell line or on primary cells.

The invention encompasses water-forming NADH and NADPH oxidases and the use of these enzymes to treat mammalian diseases or conditions associated with an elevated NADH/NAD.sup.+ ratio or NADPH/NADP+ ratio. Such pathologies include disorders caused by one or more defects in the mitochondrial respiratory chain, glucose metabolism disorders, cancers associated with reductive stress, and aging. The invention also provides a research tool for investigating the effect of exogenous water-forming NADH or NADPH oxidases on the metabolism of a mammalian cell, such as a human cell, and for elucidating the role of respiratory chain proteins in mitochondrial disorders.

Methods of treating wounds in a subject using one or both of a DNA methyltransferase 1 (DNMT1) inhibitor or a nicotinamide adenine dinucleotide phosphate oxidase 2 (NOX2) inhibitor, and compositions for use in these methods.