39 results about "Aberrant protein" patented technology

Provided herein are methods for treating conditions and disease characterized by SCN1A, SCN8A or SCN5A protein deficiency by targeting the alternative splicing events in the SCN1A gene and modulating the expression level of functional proteins in Dravet Syndrome patients and / or inhibit aberrant protein expression.

Provided herein are methods for treating conditions and diseases characterized by SCN1A, SCN8A or SCN5A protein deficiency by targeting the alternative splicing events in SCN1A gene and modulating the expression level of functional proteins in Dravet Syndrome patients and / or inhibit aberrant protein expression.

Agents that target a processed mRNA, e.g., the 5′ UTR of the processed mRNA, can modulate protein expression, e.g., via modulation of translation of the processed mRNA. Alternative splicing events in genes can lead to non-productive mRNA transcripts which in turn can lead to aberrant protein expression. Agents that target the alternative splicing events in genes can modulate the expression level of proteins. Therapeutic agents, which can modulate protein expression by targeting a processed mRNA and / or alternative splicing events, can promote functional protein expression in patients and / or inhibit aberrant protein expression. Such therapeutic agents can be used to treat a condition or disease associated with protein deficiency and / or mitochondrial function deficit.

The invention relates to methods and compositions for preventing or treating a neuropathology in a subject associated with or induced or caused by a P. gingivalis infection, preventing the deposition of or reducing the level of P. gingivalis gingipain in neuronal tissue, delaying the onset of a P. gingivalis-induced or associated neuropathology, for preventing or slowing the rate of abnormal protein deposition in the neuronal tissue, and / or reducing neuroinflammation, the methods comprising administering an RNA polynucleotide encoding a protein comprising or consisting of: - one or more amino acid sequences of an active site of an Arg- or Lys-gingipain of P. gingivalis, or a sequence that is at least 80% identical thereto; and / or - the amino acid sequence of one or more adhesin binding motifs (ABMs) of an adhesin domain of an Arg- or Lys-gingipain of P. gingivalis, or a sequence that is at least 80% identical thereto, wherein the polynucleotide is capable of being translated in a mammalian cell.

A fusion molecule having phagocytosis-inducing activity is disclosed. The fusion molecule contains a first region capable of binding a TAM receptor and a second region capable of binding to a target substance of which aberrant accumulation is associated with or characteristic of diseases. The fusion molecule effectively clears and / or reduces and / or suppresses accumulated abnormal proteins, such as beta-amyloid, tau, alpha-synuclein, huntingtin, or prion, or the like. Uses of the fusion molecule are disclosed. The fusion molecule can be used for prevention or treatment of proteinosis caused by the abnormal accumulation of substances.

Compounds, methods and pharmaceutical compositions are provided for reducing the amount or activity of PRNP RNA in cells or animals and in some cases reducing the amount of PrP protein in cells or animals. Such compounds, methods and pharmaceutical compositions can be used to improve at least one symptom or sign of neurodegenerative diseases. Such symptoms and signs are spongiform changes in the brain, formation of abnormal protein aggregates, neuronal loss, markers of neuronal loss, rapid progression dementia and death. Such neurodegenerative diseases include prion diseases, Creutzfeldt-Jakob disease (CJD), variant Creutzfeldt-Jakob disease (vCJD), familial Creutzfeldt-Jakob disease (fCJD), Gertzman-Straussler-Schinker syndrome, fatal familial insomnia, kuru, Alzheimer's disease or Parkinson's disease.

The present invention provides compositions and methods of inhibiting tyrosine phosphorylation. In one aspect, a composition comprising a low-dosage tyrosine kinase inhibitor, where the low-dosage tyrosine kinase inhibitor decreases tyrosine phosphorylation, is provided. In another aspect, a method for treating cardiovascular disease or condition associated with a RASopathy having aberrant protein tyrosine phosphorylation is described. Methods for treating congenital heart disease associated with Noonan or Noonan syndrome with multiple lentigines and decreasing aberrant levels of Protein Zero-Related (PZR) tyrosyl phosphorylation are also described.

The present invention provides a polypeptide that specifically recognizes structurally abnormal proteins generated in mammals due to misfolding or the like, and an agent for detecting or reducing structurally abnormal proteins that uses the polypeptide. The present invention relates to an agent for detecting structurally abnormal proteins, comprising as an active ingredient a polypeptide having structurally abnormal proteins-binding site which is a polypeptide consisting of the amino acid sequence represented by SEQ ID NO:2, or a polypeptide consisting of an amino acid sequence having 90% or more sequence identity with the amino acid sequence and having binding activity to structurally abnormal proteins, and an agent for reducing structurally abnormal proteins comprising as an active ingredient a polypeptide containing the structurally abnormal protein binding site and a ubiquitin ligase active site.

To provide a pharmaceutical formulation comprising trehalose for use in treating myopathies, neurodegenerative diseases, or tauopathies associated with abnormal protein aggregation.SOLUTION: A pharmaceutical formulation comprising a therapeutically effective amount of trehalose is provided, wherein the pharmaceutical formulation is for use in a method for treating a disease associated with abnormal protein aggregation and / or inclusion bodies formation in myocytes, neurons, or extracellular compartments, or for alleviating at least one symptom associated therewith in a human subject in need thereof, the method comprising intravenously administering to the subject a pharmaceutical formulation comprising 0.1% (w / v) to 50% (w / v) of trehalose. An injectable aqueous pharmaceutical formulation comprising a therapeutically effective amount of trehalose is also provided.SELECTED DRAWING: None

A variable splicing event in a gene can result in a non-productive mRNA transcript, which in turn can result in abnormal protein expression, and a therapeutic agent that can target a variable splicing event in a gene can modulate the expression level of a functional protein and / or inhibit abnormal protein expression in a patient. Such therapeutic agents are useful for the treatment of conditions or diseases caused by protein deficiency and / or mitochondrial function deficiency.

The purpose of the present invention is to suppress the effect of ultraviolet light on melanocytes. Upon performance of gene expression analysis with a focus on the olfactory receptor OR2L13 expressed by melanocytes, it was discovered that addition of (−)-carvone, a ligand of OR2L13, increased the expression of genes related to suppression of active oxygen, suppression of the production of inflammatory cytokines or chemokines, suppression of senescence, and / or degradation of abnormal proteins. As a result of said discovery, the present invention provides an inhibitor of the effects of ultraviolet light on melanocytes that includes (−)-carvone.

Alternative splicing events in genes can lead to non-productive mRNA transcripts which in turn can lead to aberrant or reduced protein expression, and therapeutic agents which can target the alternative splicing events in the genes can modulate the expression level of functional proteins in patients and / or inhibit aberrant protein expression. Such therapeutic agents can be used to treat a condition or disease caused by protein deficiency.

Disclosed is a method of treatment of a disease associated with abnormal protein aggregation comprising parenterally administering pharmaceutical formulations comprising trehalose. Also disclosed is an injectable aqueous pharmaceutical formulation comprising a therapeutically effective amount of trehalose.

The present invention relates to a novel peptide and its use, and more specifically, to a peptide having the ability to inhibit the formation of abnormal protein aggregates, having the ability to inhibit the formation of abnormal protein aggregates and autophagy activity against the protein aggregates, H-G-X 1 -X 2 -G-X 3 which comprises a structure of, and provides a novel peptide having a length of 4 to 10 amino acids and its use.

Diagnostic and therapeutic methods for neurodegenerative diseases. Are provided involving assaying abnormal proteins (hyperphosphorylated tau, α-synuclein, TDP-43) associated with neuronal turnover inhibition or promotion in patient samples. Abnormal protein expression and apoptotic activity are detected, aiding disease progression assessment. Therapeutically, a method is provided for treating neurodegenerative diseases, administering compounds promoting neuronal turnover or modulating proteins involved in the process. The invention extends to identifying suitable drugs, employing neuronal turnover induction, miRNA modulation, and protein activity inhibition or enhancement. The claims also encompass various species, tissues, and cultured cells. Furthermore, the invention is applicable to diverse neurodegenerative diseases with abnormal protein accumulation, presenting novel diagnostic and treatment approaches.

Described herein are polypeptide useful for identifying compound for modulating aberrant protein condensates. The polypeptide comprise a condensate-modulating protein, a first biomarker polypeptide, a barcoding biomarker polypeptide. When inside a cell, the non-natural polypeptide exist as multiple fragments, including a first fragment comprising the condensate-modulating protein and the first biomarker polypeptide, and a second fragment comprising the barcoding biomarker polypeptide. The barcoding biomarker polypeptide is uniquely associated with and identifies the cell expressing associated condensate-modulating protein. Also described is a polynucleotide encoding the non-natural polypeptide, a library of the polynucleotide, and a method of identifying compound for modulating aberrant protein condensates using the non-natural polypeptide, the construct, and / or the library.

The invention relates to a magnetic activation preparation method and application of phagocytic anti-inflammatory phenotype microglial cells, and the method comprises the following steps: separating and culturing microglial cells, and after the cells are cultured to a preset fusion degree, stimulating the microglial cells by using a pulsed magnetic field to obtain high-phagocytic and high-anti-inflammatory phenotype microglial cells which are transplanted into a specific brain region, the pulse magnetic field is used for treating central nervous cell diseases, the stimulation frequency of the pulse magnetic field is 1-100 Hz, the number of stimulation pulses is larger than or equal to 500, and the number of stimulation days is larger than or equal to 1 day. The microglial cells obtained by adopting low-frequency pulse stimulation have stronger migration ability, can swallow more foreign matters or abnormal protein aggregation products, can secrete less proinflammatory factors, is beneficial to recovery of the microenvironment of the central nervous system, and can be used for improving the microenvironment of the central nervous system. The invention provides an efficient, accurate and economical new way for microglial cells to treat neuroinflammation regulation and control and abnormal protein aggregation related diseases, and solves the technical problems of large side effect, high cost, inaccurate target spot, difficulty in acting on deep microglial cells and the like in the prior art.

To provide a method of treating a cardiovascular disease or condition having aberrant protein tyrosine phosphorylation.SOLUTION: The method comprises administering a low-dosage of a tyrosine kinase inhibitor to a subject, where the tyrosine kinase inhibitor decreases aberrant levels of tyrosine phosphorylation and improves at least one cardiac function in the subject. Preferably, the tyrosine kinase inhibitor is selected from the group consisting of afatinib, axitinib, bosutinib, cabozantinib, cediranib, ceritinib, crizotinib, dabrafenib, dasatinib, and the like.SELECTED DRAWING: Figure 1A

Disclosed are immunomodulatory compounds, pharmaceutical compositions containing them, and methods of making and using the compounds to treat diseases and disorders characterized by aberrant protein activity that can be targeted by cereblon.

Alternative splicing events in genes can lead to non-productive mRNA transcripts which in turn can affect protein expression level, and therapeutic agents which can target the alternative splicing events in genes can modulate the expression level of functional proteins in patients and / or inhibit aberrant protein expression. Such therapeutic agents can be used to treat a condition or disease caused by protein deficiency.

Alternative splicing events in genes can lead to nonproductive mRNA transcripts which in turn can lead to aberrant protein expression, and therapeutic agents which can target the alternative splicing events in genes can modulate the expression level of functional proteins in patients and / or inhibit aberrant protein expression. Such therapeutic agents can be used to treat a condition or disease caused by protein deficiency and / or mitochondrial function deficit.

The present invention provides compositions and methods of inhibiting tyrosine phosphorylation. In one aspect, a composition includes comprising a low-dosage tyrosine kinase inhibitor, where the low-dosage tyrosine kinase inhibitor decreases tyrosine phosphorylation. In another aspect, a method is described for treating cardiovascular disease or condition associated with a RASopathy having aberrant protein tyrosine phosphorylation. Methods for treating congenital heart disease associated with Noonan or Noonan syndrome with multiple lentigines and decreasing aberrant levels of Protein Zero-Related (PZR) tyrosyl phosphorylation are also described.

Provided is an agent for inhibiting abnormal protein aggregate accumulation or an agent for inhibiting the uptake of an abnormal protein into a neuron, particularly an agent for preventing or treating a disease associated with accumulation of abnormal protein aggregates, in which the agent contains an RGMa inhibiting substance.

The present disclosure relates to a peptide for inhibiting PPI between IP3R and GRP75 in MAM, and a composition for preventing, alleviating or treating a disease related to autophagy disorder containing the same as an active ingredient.The features and advantages of the present disclosure may be summarized as follows:(a) The present disclosure provides a peptide capable of inducing intracellular autophagy by inhibiting the interaction between the endoplasmic reticulum and mitochondria, more specifically the PPI between IP3R and GRP75 in MAM, by regulating the activity of MAM.(b) The peptide of the present disclosure can be usefully applied to alleviate or treat a disease related to autophagy disorder, especially a disease caused by abnormal protein accumulation induced by reduced intracellular autophagy or a degenerative disease.

The invention belongs to the technical field of biology, and particularly relates to a composition for improving the developmental potential of oocytes, an in-vitro maturation culture solution and an optimized culture method. And a CCR5 / CXCR3 antagonist. The preparation for in-vitro embryo production contains an Ephrin ligand family and a CCR5 / CXCR3 antagonist, the microenvironment for maturation culture of oocytes is synergistically optimized, further, sesquiterpenol compounds and / or phenylpropane compounds can be added on the basis, and therefore the preparation can be used for preparing the embryos in vitro by means of the synergistic effect of the components. The composition can effectively inhibit the formation of abnormal protein aggregates in oocytes, enhance the ability of proteasomes to remove error protein aggregates, significantly reduce the level of reactive oxygen species (ROS) and increase the content of endogenous antioxidant substances such as glutathione (GSH), so as to reduce the protein toxicity stress, oxidative stress and other dimensions, and thus, the composition can be used for preparing an anti-inflammatory drug. The quality and the fertilization rate of oocytes after in-vitro maturation and the development potential of subsequent embryos are remarkably improved, and the application prospect is wide.

The disclosure provides pharmaceutical compositions comprising Efruxifermin, processes for preparing lyophilized compositions, and methods of use for treating nonalcoholic steatohepatitis (NASH), nonalcoholic fatty liver disease (NAFL), alcoholic steatohepatitis (ASH), alcoholic liver disease (ALD) or alcoholic fatty liver disease (AFL), type 2 diabetes, obesity, hypertriglyceridemia, dyslipidemia, protein misfolding disease, alcohol-related and other cravings or addictions, reversing liver cirrhosis or reducing fibrosis associated with NASH, ASH, ALD AFL, or protein misfolding disease, normalizing liver fat content, reducing elevated blood glucose, increasing insulin sensitivity, and / or reducing uric acid levels.

Alternative splicing events in genes can lead to non-productive mRNA transcripts which in turn can lead to aberrant protein expression, and therapeutic agents which can target the alternative splicing events in genes can modulate the expression level of functional proteins in patients and / or inhibit aberrant protein expression. Such therapeutic agents can be used to treat a condition or disease caused by protein deficiency.

Alternative splicing events in genes can lead to non-productive mRNA transcripts which in turn can lead to aberrant protein expression, and therapeutic agents which can target the alternative splicing events in genes can modulate the expression level of functional proteins in patients and / or inhibit aberrant protein expression. Such therapeutic agents can be used to treat a condition or disease caused by protein deficiency and / or mitochondrial function deficit.

Disclosed is a method of treatment of a disease associated with abnormal protein aggregation comprising parenterally administering pharmaceutical formulations comprising trehalose. Also disclosed is an injectable aqueous pharmaceutical formulation comprising a therapeutically effective amount of trehalose.

The purpose of the present invention is to suppress the effect of ultraviolet light on melanocytes. Upon performance of gene expression analysis with a focus on the olfactory receptor OR2L13 expressed by melanocytes, it was discovered that addition of (−)-carvone, a ligand of OR2L13, increased the expression of genes related to suppression of active oxygen, suppression of the production of inflammatory cytokines or chemokines, suppression of senescence, and / or degradation of abnormal proteins. As a result of said discovery, the present invention provides an inhibitor of the effects of ultraviolet light on melanocytes that includes (−)-carvone.