The present invention relates to methods of activate an isoform of protein kinase C (PKC) for the treatment of neurological diseases including Alzheimer's disease and stroke using cyclopropanated or epoxidized derivatives of mono- and polyunsaturated fatty acids. The present invention also relates to methods of reducing neurodegeneration using cyclopropanated or epoxidized derivatives of mono- and polyunsaturated fatty acids.

The disclosed invention relates to methods of modifying peptide compositions to increase stability and delivery efficiency. Specifically, the disclosed invention relates to methods to increase the stability and delivery efficiency of protein kinase C (PKC) modulatory peptide compositions. A “therapeutic peptide composition” comprises a “carrier peptide” and a “cargo peptide.” A “carrier peptide” is a peptide or amino acid sequence within a peptide that facilitates the cellular uptake of the therapeutic peptide composition. The “cargo peptide” is a PKC modulatory peptide. Peptide modifications to either the carrier peptide, the cargo peptide, or both, which are described herein increase the stability and delivery efficiency of therapeutic peptide compositions by reducing disulfide bond exchange, physical stability, reducing proteolytic degradation, and increasing efficiency of cellular uptake.

The present invention relates to methods of activate an isoform of protein kinase C (PKC) for the treatment of neurological diseases including Alzheimer's disease and stroke using cyclopropanated or epoxidized derivatives of mono- and polyunsaturated fatty acids. The present invention also relates to methods of reducing neurodegeneration using cyclopropanated or epoxidized derivatives of mono- and polyunsaturated fatty acids.

Disclosed is a Designer Receptor Exclusively Activated by Designer Drugs (DREADD), and an amino acid sequence for determining coupling or no coupling between G-protein and G-protein coupled receptor (GPCR) mediated by a GPCR ligand in a cell based assay.

The present invention relates to calcium dependent protein kinase (CORK) constructs comprising a pair of chromophores suitable for measuring real-time FRET occurrence upon conformational changes or activation of the CORK construct. Particularly, the present invention relates to CORK polypeptides comprising a variable domain (VD), a protein kinase domain (PKD), a pseudosubstrate segment (PS), and a calmodulin-like domain (OLD), said CLD comprising 4 EF-hand motifs EF1, EF2, EF3 and EF4, wherein a donor chromophore is inserted between PKD and PS and an acceptor chromophore is inserted C-terminally of EF4, or an acceptor chromophore is inserted between PKD and PS and a donor chromophore is inserted C-terminally of EF4, wherein said donor chromophore and said acceptor chromophore represent a Förster Resonance Energy Transfer (FRET) pair. The present invention further relates to polynucleotides encoding such polypeptides as well as vectors and host cells comprising such polypeptides and/or polynucleotides. Furthermore, the present invention relates to methods for measuring conformational change or activation status of a CDPK polypeptide by employing said polypeptides and to uses of said polypeptides for measuring conformational change or activation status of a CDPK polypeptide.

The present invention relates to a method for identifying a target protein using a thermal stability shift-based fluorescence difference in two-dimensional gel electrophoresis, and more specifically, a method for identifying a protein, which is a target of a specific drug, by analyzing, by means of a fluorescence difference in two-dimensional gel electrophoresis, a thermal stability shift in the protein when a specific drug, preferably a bioactive molecule, binds to the target protein.

The present invention relates to novel peptides, compositions and uses thereof useful in tissue permeabilization, in particular in the context of treatment of cancer prevention and/or treatment or induction of an immune response, in particular via mucosal vaccination or anti-opioid treatment.

The invention pertains to a method of treating melanoma by administering to a subject in need thereof, a composition comprising a therapeutically effective amount of an inhibitor of PKC-ζ and/or PKC-.Math.. Non-limiting examples of an inhibitor of PKC-ζ and/or PKC-.Math. include ICA-1 and ACPD. The invention also provides PKC-ζ and/or PKC-.Math. as biomarkers for identifying a melanoma in a subject as likely to be responsive or non-responsive to a therapy using an inhibitor of PKC-ζ and/or PKC-.Math.. Accordingly, a method of identifying a subject having a melanoma as being responsive or non-responsive to a melanoma therapy with an inhibitor of PKC-ζ and/or PKC-.Math. based on the levels and/or activity of PKC-ζ and/or PKC-.Math. mRNA or protein in the melanoma cells from the subject are also provided.

The present invention relates to peptides for the treatment or prevention of nonalcoholic fatty liver disease (NAFLD), non-alcoholic fatty liver (NAFL), non-alcoholic steatohepatitis (NASH), hepatic steatosis (fatty liver), liver inflammation, cirrhosis, hepatocellular carcinoma or fibrosis, especially liver fibrosis.

The invention pertains to a method of treating melanoma by administering to a subject in need thereof, a composition comprising a therapeutically effective amount of an inhibitor of PKC- and/or PKC-.Math.. Non-limiting examples of an inhibitor of PKC- and/or PKC-.Math. include ICA-1 and ACPD. The invention also provides PKC- and/or PKC-.Math. as biomarkers for identifying a melanoma in a subject as likely to be responsive or non-responsive to a therapy using an inhibitor of PKC- and/or PKC-.Math.. Accordingly, a method of identifying a subject having a melanoma as being responsive or non-responsive to a melanoma therapy with an inhibitor of PKC- and/or PKC-.Math. based on the levels and/or activity of PKC- and/or PKC-.Math. mRNA or protein in the melanoma cells from the subject are also provided.