14 results about "Hyperphosphorylation" patented technology

The present invention relates to a novel heteroaryl-carbohydrazone acyldinitrile compound in which a saturated heterocyclic ring is substituted or a pharmaceutically acceptable salt thereof, a method for preparing the same, and a pharmaceutical composition for preventing or treating nervous system diseases comprising the same as an active ingredient. The heteroaryl-carbohydrazone acyldinitrile compound with a substituted saturated heterocyclic ring according to the present invention can effectively inhibit the aggregation or excessive phosphorylation of Tau protein and / or TDP-43, thereby being useful in the prevention or treatment of nervous system diseases including Tau disease and TDP-43 proteopathy.

The present invention relates to a method for preparing an ethanol extract of Ecklonia cava, and a composition for preventing, alleviating or treating cognitive dysfunction, comprising same as an active ingredient. The ethanol extract of Ecklonia cava, of the present invention, contains phlorotannin oligomer, eckol, 7-phloroeckol, 6,6'-bieckol, 6,8'-bieckol, dibenzodioxin-fucodiphlorethol, diekcol, phlorofuroeckol A and 2,7''- phloroglucinol-6,6'-bieckol in ratios of 1-2 : 5-6 : 6.5-7.5 : 7-8 : 20-21 : 3-4 : 47-48 : 4.5-5.5 : 1.5-2.5, respectively, has excellent effects of improving behavioral function, improving antioxidant system, improving mitochondrial function, improving cholinergic system, alleviating toxicity caused by Aβ aggregation and Tau hyperphosphorylation, improving inflammation and inhibiting cell death, and thus can be effectively used as a pharmaceutical composition or health functional food composition for preventing, alleviating, or treating cognitive dysfunction.

This invention discloses the use of cyanidin anthocyanins or their pharmaceutically acceptable salts, esters, and solvates in the preparation of drugs for the prevention and / or treatment of neurodegenerative diseases. The cyanidin anthocyanins are selected from cyanidin-3-O-rutin glycoside, cyanidin-3-O-sophoroside, or cyanidin-3-O-xyloside. These compounds can inhibit acetylcholinesterase activity, upregulate α7 nicotinic acetylcholine receptor expression, and activate the PI3K / AKT / GSK3β signaling pathway, thereby inhibiting Tau protein hyperphosphorylation and reducing neuroinflammatory responses. Furthermore, it has been confirmed that cyanidin-3-O-rutin glycoside directly binds to acetylcholinesterase, verifying AChE as its key target, providing new natural active compounds and their mechanisms of action for the prevention and treatment of neurodegenerative diseases.

The present invention relates to a method for the in vitro diagnosis of a neurodegenerative disease in a human or animal individual in the early stage, comprising a step comprising the detection of the presence of at least one marker selected from the group consisting of derived forms of amyloid beta (A beta) peptides, the derivative forms are selected from oligomers of the peptide and pre-fibrotic and fibrotic aggregated forms of the peptide, and derivative forms of a phosphorylated tau protein, and the derivative forms are selected from over-phosphorylated forms of the protein, aggregated forms of the protein and modified phosphorylated tau proteins resulting from one or more post-translational modifications; the presence of a marker is detected in a fecal sample of the individual.

The present invention provides a medicine for treating a neurodegenerative disease, which employs LEFTY2 (Left-Right Determination Factor 2) generated by co-culturing mesenchymal stem cells of mammals with nerve cells having mutations in the APP (Amyloid precursor protein) gene, or a specific protein. The LEFTY2 has an effect of inhibiting Beta amyloid and a hyperphosphorylated neuronal microtubule-associated protein (Tau protein), without affecting the development of nerve cells and having the ability to promote the growth of the nerve cells; and the two types of proteins have a crucial impact on the neurodegenerative diseases.

The invention discloses fructus alpiniae oxyphyllae-derived extracellular vesicle-like nanoparticles as well as a preparation method and application thereof. The preparation method comprises the following steps: soaking a fructus alpiniae oxyphyllae raw material, breaking walls, crushing, centrifugally filtering, concentrating by tangential flow, centrifuging in multiple stages, filtering and the like. According to the preparation method provided by the invention, differential centrifugation is combined with a tangential flow concentration technology, so that the extracellular vesicle-like nanoparticles can be efficiently and completely enriched and purified from the fructus alpiniae oxyphyllae. The whole process is carried out at low temperature, so that the biological activity of the vesicles is protected to the greatest extent, the use of an organic solvent is avoided, and the naturalness and safety of the product are ensured. According to the fructus alpiniae oxyphyllae-derived nanoparticles, by activating IRS-1, promoting PI3K activation, increasing PIP3 generation and activating Akt, GSK-3beta is subjected to phosphorylation to inactivate GSK-3beta, excessive phosphorylation and accumulation of Tau protein are reduced, and plaque formation is delayed. In a diabetic cognitive impairment model, the nanoparticles have a remarkable neuroprotective effect and can improve the cognitive function and reduce inflammatory response.

The present application relates to the technical field of gene editing, in particular to a construction method of an Alzheimer's disease model pig based on endogenous multi-gene editing. APP KM652 / 653NL 、 PSEN1 M143L and TAU P300L PegRNA and nick-sgRNA of the site, using an optimized editing system, achieving simultaneous precise editing of three endogenous gene sites in pigs, successfully obtaining an Alzheimer's disease model pig based on endogenous multi-gene simultaneous editing. The cloned pig can reproduce the characteristic Aβ deposition gene and Tau protein hyperphosphorylation double pathology phenotype of Alzheimer's disease, and can be applied to drug screening, pathological mechanism research, target verification and biomarker development of Alzheimer's disease, and has a wide application prospect.

The invention belongs to the technical field of biological medicines, and particularly relates to application of a DOK6 related biological product in preparation of a medicine for treating or relieving Alzheimer's disease. It is found that abnormal activation of NLRP3 induced by intestinal inflammation causes pathological increase of IL-1beta in peripheral blood, then NLRP3 inflammasomes of microglial cells in the brain are activated, expression of NT-3 is lowered in the process, the function of DOK6 in neuronal cells is weakened, a DOK6-TrkC compound is dissociated, MEK / ERK1 / 2 channels are abnormally activated, Tau protein is excessively phosphorylated, and accordingly the NLRP3 inflammasomes are activated. Reverse axon transportation collapse is promoted, neuronal axon mutagenicity is caused to mediate secondary myelin sheath injury, and the progress of the Alzheimer disease is accelerated; and after the DOK6 related biological product for promoting the expression of the nerve center DOK6 is utilized, the molecular pathological cascade reaction of the Alzheimer's disease can be reversed, so that the prevention and treatment of the Alzheimer's disease can be realized.

The invention provides a neuroprotective effect of DIRAS1 on Alzheimer's disease (AD), and belongs to the technical field of biological medicine. The invention provides application of a reagent for overexpressing a DIRAS1 gene in preparation of a medicine for preventing and / or treating AD by taking the DIRAS1 gene as a therapeutic target of AD. The treatment of a model mouse in the embodiment finds that the DIRAS1 gene is over-expressed in the brain of the AD mouse, and the cognitive function detection finds that the recognition memory, the working memory and the long-term spatial learning memory of the AD mouse can be remarkably improved; morphological and molecular biological detection finds that deposition of A beta and excessive phosphorylation of Tau protein are reduced, and Golgi staining and western blot detection finds that damage to a synaptic structure is reduced and expression of synaptic related protein is increased. Therefore, the cognitive function, pathological characteristics and synaptic plasticity of AD mice can be improved by a method of overexpressing the DIRAS1 gene.

The application provides a circular RNA circ_0004801 and application thereof in Alzheimer's disease treatment; a nucleotide sequence of the circular RNA circ_0004801 is shown as SEQ ID NO:1. Expression of the circular RNA circ_0004801 in hippocampus tissue of AD mice is significantly up-regulated, the circular RNA circ_0004801 acts as a "sponge" of miR-7688-5p, and plays a role by regulating TTBK1 expression and tau phosphorylation level. Knocking down the circular RNA circ_0004801 can obviously improve spatial learning and memory of 3xTg mice, significantly reduce tau protein phosphorylation level in hippocampus and NFTs density in hippocampus DG region. Therefore, the circular RNA circ_0004801 and miR-7688-5p can be used as a new target for treating AD. The application first finds that the circular RNA circ_0004801 regulates TTBK1 through a ceRNA mechanism, thereby driving tau hyperphosphorylation, and provides a new molecular target for early intervention treatment of AD based on circRNA and miRNA.

This application relates to the field of medicinal chemistry, specifically to a derivative of ligustilide-7-aminocarbamate-4'-substituted aminopropyl ether, its preparation method, and its application. Addressing the shortcomings of ligustilide in AD treatment, this application utilizes previous studies to demonstrate strong eeAChE and huACh inhibitory activity, strong inhibition of self-induction, and Cu... 2+ Induced Aβ 1‑42 Aggregation activity, significantly reduced Aβ 25‑35 The lead compound, scutellarin aglycone-4′-L-amino acid carbamate, which induces tau hyperphosphorylation and significantly improves learning and memory impairment in scopolamine-induced AD model mice, is used to introduce histamine H at the 7-position of its structure. 3 By using the key structural fragment (3-methylpiperidinyl) or cycloheptane group of the receptor antagonist, a cholinesterase inhibitor and histamine H2 receptor antagonist can be obtained. 3 Multi-targeted ligand derivatives with better anti-AD properties through receptor antagonistic synergistic mechanism.

The invention is applicable to the technical field of biological medicines, and provides application of a YAP agonist in preparation of a medicine for treating intestinal lymphatic vessel dysfunction. The invention analyzes the molecular mechanism of improving high fat diet induced lymphatic vessel dysfunction through targeted regulation of VEGFR3 / YAP / mTOR signaling pathways and the treatment application of the YAP agonist, the YAP agonist recovers the nuclear translocation ability through antagonism of YAP excessive phosphorylation, and activates the mTOR signaling pathways, so that the proliferation, migration and tube formation functions of LECs are remarkably improved, and the treatment effect of the YAP agonist on the lymphatic vessel dysfunction induced by high fat diet is improved. Meanwhile, VE-cadherin expression is up-regulated so as to repair the integrity of the endothelial barrier; the YAP agonist can effectively relieve intestinal lymphatic vessel dysfunction and structural abnormality induced by HFD.

The invention belongs to the technical field of biological medicines, and particularly relates to application of a reagent for detecting the expression level of SOCS3 in preparation of a product for evaluating the treatment effect of mesenchymal stem cells on pulmonary arterial hypertension. By integrating transcriptomics and functional experiments, the invention reveals that MSC activates the expression of SOCS3 through paracrine, and further inhibits the excessive phosphorylation of STAT3, thereby blocking the molecular mechanism of PAAF activation and ECM abnormal deposition. The expression level of the SOCS3 can be used as a marker for judging the inhibition of the mesenchymal stem cells on the activation of the pulmonary adventitia fibroblasts, and also can be used as a marker for judging the treatment effect of the mesenchymal stem cells on the pulmonary arterial hypertension. By up-regulating the expression of SOCS3, the excessive phosphorylation of STAT3 can be inhibited, the activation of pulmonary outer membrane fibroblasts and the expression of Col1 and Col3 can be inhibited, but the proliferative activity is not influenced, so that the PAH can be treated.

The present application is suitable for the field of biological medicine technology, and provides application of a YAP agonist in preparation of a drug for treating intestinal lymphatic vessel dysfunction. The present application analyzes a molecular mechanism of the YAP agonist in improving high-fat diet induced lymphatic vessel dysfunction through targeted regulation of a VEGFR3 / YAP / mTOR signal pathway and a therapeutic application thereof, the YAP agonist antagonizes excessive phosphorylation of YAP, restores the nuclear translocation ability of YAP, activates the mTOR signal pathway, significantly improves the proliferation, migration and tube formation functions of LECs, and up-regulates VE-cadherin expression to repair endothelial barrier integrity; the YAP agonist can effectively relieve intestinal lymphatic vessel dysfunction and structural abnormalities induced by HFD.