9 results about "Tau phosphorylation" patented technology

The invention provides a circular RNA circ0004801 and an application of the circular RNA circ0004801 in treatment of an Alzheimer's disease. The nucleotide sequence of the circular RNA circ0004801 is as shown in SEQ ID NO: 1 (Sequence Identity Number 1). The expression of the circular RNA circ0004801 in the hippocampal tissue of the AD mouse is obviously up-regulated, and the circular RNA circ0004801 is used as a'sponge 'of miR-7688-5p and plays a role by adjusting the TTBK1 expression and tau phosphorylation level. By knocking down the circular RNA circ0004801, the spatial learning and memory of a 3 * Tg mouse can be obviously improved, and the tau protein phosphorylation level of a hippocampus region and the NFTs density of a hippocampus DG region can be obviously reduced. Therefore, the circular RNA circ0004801 and the miR-7688-5p can be used as new targets for treating the AD (Alzheimer's disease). According to the invention, it is found for the first time that circular RNA circ0004801 regulates TTBK1 through a ceRNA mechanism, so that excessive phosphorylation of tau is driven, and a new molecular target is provided for AD early intervention treatment based on circRNA and miRNA.

This invention relates to the field of organoid disease models, and discloses a method for constructing a human brain organoid model of early-onset Alzheimer's disease (AD) and its applications. This invention introduces [a specific technology] into human embryonic stem cell lines through single-base editing and lead editing techniques. PSEN1 ΔE9、 PSEN1 M146V and APP Human embryonic stem cell lines carrying four familial pathogenic gene mutations (K670N and M671L) were constructed and induced to differentiate into Alzheimer's disease (AD) brain organoids. The AD brain organoid model established by this invention exhibited tau phosphorylation pathological phenotypes as early as 20 days and Aβ-related phenotypes as early as 40 days, with increased total Aβ, decreased Aβ42 / Aβ40 ratio, and simultaneous aggravation of Aβ-Tau pathology. This represents a complex neurodegenerative pathological model where multiple mutations synergistically regulate Aβ production and tau phosphorylation, which is highly valuable for understanding and studying early-onset familial AD. This invention provides a human brain organoid model for in vitro AD studies and offers a tool for studying the pathological mechanisms of AD and screening drugs.

The invention discloses application of human dental pulp stem cells in enhancing neurogenesis in a brain region and treating neurodegenerative diseases, including stem cells for enhancing neurogenesis of adult hippocampus, and the human dental pulp stem cells have the following functional characteristics: flow cytometry detection shows that the Netin positive rate is not lower than 90%, and the beta-tubulin III positive rate is not lower than 85%; in a conditioned culture medium after in-vitro culture for 24 hours, the secretion amount of BDNF reaches more than 500pg / mL / 106 cells, and the secretion amount of GDNF reaches more than 200pg / mL / 106 cells; the alizarin red dyeing positive area accounts for not less than 60% after osteogenesis induction, and the oil red O dyeing positive area accounts for not less than 50% after adipogenesis induction; according to the quantitative standard that the number of dentate gyrus DCX + newborn neurons of the adult hippocampus is increased by more than 50% compared with that before treatment, the dual-mechanism targeted therapy 1 specifically activates hippocampus neural stem cells and promotes newborn neurons to differentiate by highly expressing neural markers and secreting neurotrophic factors, so that the neurogenesis of the adult hippocampus is enhanced, and the neurogenesis of the adult hippocampus is enhanced. Meanwhile, A beta deposition and p-Tau phosphorylation are reduced.

The invention discloses application of DDC silencing in an encephalatrophy model, and relates to the field of traumatic brain injury. According to the application, by inhibiting DDC gene expression or protein activity, GSK-3beta kinase mediated Tau protein phosphorylation is regulated and controlled, so that encephalatrophy is relieved or prevented; wherein the encephalatrophy model is an immature brain traumatic brain injury (TBI) after-encephalatrophy model, and DDC silencing is achieved through siRNA, shRNA or antisense oligonucleotide. A gene expression profile after immature brain TBI is analyzed through transcriptome sequencing, DDC is found to be remarkably up-regulated and enriched in a 5-hydroxytryptamine synaptic pathway, an in-vivo experiment proves that DDC expression and Tau phosphorylation level are synchronously increased, an in-vitro experiment shows that DDC silently inhibits GSK-3beta-mediated Tau phosphorylation, and a basis is provided for a DDC-targeted treatment strategy.

The invention discloses a method for diagnosing and treating AD (Alzheimer's disease) by recognizing olfactory disorder through PET (Polyethylene Terephthalate). The method comprises the following steps: (1) observing olfactory and cognitive behavioral changes of AD mice, and evaluating olfactory and cognitive function conditions of the 3 * Tg mice by carrying out behavioral experiments on the 12-month-old 3 * Tg mice; and (2) quantifying A beta in the intracranial olfactory related area of the AD mouse through PET imaging, performing A beta-PET imaging on a 12-month-old 3xTg mouse, reconstructing a PET image through a PET / CT scanner, performing SUV quantification on the intracranial olfactory related area, and observing the deposition condition of the A beta in the olfactory related area. And (3) observing A beta and tau phosphorylation expression and distribution conditions of AD mice in pathology, observing A beta expression and distribution conditions in brains of 12-month-old 3xTg mice through immunofluorescence, dividing olfaction-related regions by referring to an Allen mouse brain map, observing expression conditions of A beta in the olfaction-related regions, and calculating average fluorescence intensity of each region for semi-quantitative analysis.

A method of inhibiting phosphorylation of the tau protein and / or a TLR4-mediated immune response is disclosed. The method contemplates administering to cells in recognized need thereof such as cells of the central nervous system an effective amount of a of a compound or a pharmaceutically acceptable salt thereof that binds to a pentapeptide of filamin A (FLNA) of SEQ ID NO: 1, and contains at least four of the six pharmacophores of FIGS. 35-40.

The present disclosure provides methods to quantify tau phosphorylation at specific amino acid residues, using blood samples, to predict time to onset of mild cognitive impairment due to Alzheimer's disease, stage Alzheimer's disease, guide treatment decisions, select subjects for clinical trials, and evaluate the clinical efficacy of certain therapeutic interventions.

A method of inhibiting phosphorylation of the tau protein and / or a TLR4-mediated immune response is disclosed. The method contemplates administering to cells in recognized need thereof such as cells of the central nervous system an effective amount of a of a compound or a pharmaceutically acceptable salt thereof that binds to a pentapeptide of filamin A (FLNA) of SEQ ID NO: 1, and contains at least four of the six pharmacophores of FIGS. 35-40.

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.