121 results about "Nuclear protein" patented technology

The invention belongs to the technical field of biological detection, and relates to an antibody composition aiming at human pS129-alpha-Syn protein detection and application thereof, and the antibody composition comprises a targeted pS129-alpha-Syn protein phosphorylation antibody and a targeted human alpha-synuclein N-terminal antibody. Meanwhile, based on the antibody composition for detecting the human pS129-alpha-Syn protein, the invention further provides a kit for early diagnosis of the Parkinson's disease. The invention provides an antibody composition aiming at human pS129-alpha-Syn protein detection and application of the antibody composition. The antibody composition is higher in detection specificity and sensitivity.

The invention discloses recombinant xanthomonas campestris with xanthan gum hydrolase displayed on the surface and a construction method and application of the recombinant xanthomonas campestris. The recombinant xanthomonas campestris for surface display of xanthan hydrolase is constructed by introducing a recombinant vector obtained by fusion expression of an ice crystal nuclein (INP) gene and a xanthan hydrolase gene into xanthomonas campestris. The gel yield of recombinant xanthomonas campestris fermentation is twice that of a wild strain and reaches 6.7 g / L. The strain can efficiently hydrolyze xanthan gum with high molecular weight (such as more than 100 wDa), the traditional production process which is relatively complicated is simplified, and a new method is provided for large-scale production of the xanthan gum with low molecular weight.

Compounds and compositions comprising compounds that modulate histone acyltransferase (HAT). Methods of treating neurodegenerative disorders, conditions associated with amyloid-beta peptide deposit accumulation, Tau protein levels, and / or alpha-synuclein accumulation, and cancer by administering to a subject a compound that modulates HAT.

Provided herein is a method comprising: binding α-synuclein to a biolayer interferometry (BLI) microprobe, contacting the BLI microprobe with a biological sample, contacting the BLI microprobe with α-synuclein, and measuring an optical signal from the BLI microprobe, wherein the optical signal indicates whether α-synuclein aggregates have formed on the microprobe.

The invention relates to application of 1-allyl piperazine or pharmaceutically acceptable salt thereof in preparation of a medicine for treating Parkinson's disease. A caenorhabditis elegans PD model is adopted to prove for the first time that on one hand, 1-allyl piperazine can obviously enhance autophagy activity in a model animal body, efficiently promote removal of aggregation alpha-synuclein and radically relieve damage of Parkinson's disease characteristic pathological protein deposition to neurons, and on the other hand, 1-allyl piperazine can effectively promote removal of aggregation alpha-synuclein and radically relieve damage of Parkinson's disease characteristic pathological protein deposition to neurons. The compound can effectively activate mitochondrial unfolded protein reaction. The autophagy activation pathway and the mitochondrial function regulation pathway can generate a synergistic effect to jointly relieve the neurodegeneration process related to the Parkinson's disease, so that dopaminergic neurons are protected, and the pathological progress of the disease is delayed.

The present invention relates to novel molecules that can be employed for the prevention, alleviation, treatment and / or diagnosis of diseases, disorders and abnormalities associated with alpha-synuclein (α-synuclein, A-synuclein, aSynuclein, A-syn, α-syn, aSyn, a-syn) aggregates, including, but not limited to, Lewy bodies and / or Lewy neurites, such as Parkinson's disease, Multiple System Atrophy, Lewy Body dementia (LBD; dementia with Lewy bodies (DLB) (“pure” Lewy body dementia), Parkinson's disease dementia (PDD)) or Diffuse Lewy Body Disease. The invention relates to alpha-synuclein binding molecules, in particular to alpha-synuclein antibodies or an antigen-binding fragment or a derivative thereof and uses thereof. The present molecules can also be used for determining a predisposition to such a disorder, disease or abnormality, monitoring residual disorder, disease or abnormality, or predicting the responsiveness of a patient who is suffering from such a disorder, disease or abnormality to treatment with a certain medicament.

Disclosed is a method of treating a neurodegenerative disease such as Parkinson's disease, diffuse Lewy body disease, transitional Lewy body dementia, and multiple system atrophy in a subject. The method comprises administering to the subject a therapeutically effective amount of a peptide comprising an α-synuclein binding domain operably linked to a protein transduction domain and a proteasomal targeting domain, wherein the α-synuclein binding domain is derived from a reversed sequence of β-synuclein. Other methods, as well as uses and compositions, are disclosed.

The present application relates to the field of medical detection, in particular to a detection reagent, a detection kit and a detection method of amyloid aggregates. The present application provides a seed amplification test method of pathological alpha-synuclein aggregates, which coats or fixes specific anti-alpha-Syn antibodies on the bottom and side of an enzyme-labeled plate, captures pathological alpha-Syn aggregates in the sample, washes off unbound alpha-Syn or other substances, effectively removes various interference amplification factors in the sample, and incubates and amplifies in a buffer containing alpha-Syn monomers in a vibration-intermittent vibration cycle. In the initial stage of SAA amplification, the pathological alpha-Syn aggregates as seeds are adsorbed to the interface between the solid phase and the liquid phase with the maximum shear stress, greatly increasing the alpha-Syn aggregation efficiency, shortening the lag time in the initial stage, greatly shortening the amplification time, and solving the problems existing in the current alpha-Syn-SAA test.

The invention belongs to the technical field of animal model construction, and particularly relates to a mouse model based on alpha-synuclein mutation and a construction method and application thereof. The mouse Snca gene is subjected to site-specific modification and mutates at the site S129A, S129D or Y125F, an alpha-syn mutation animal model which does not need exogenous induction and can naturally develop typical PD pathology and behavior phenotypes is constructed, and the limitation of an existing model in the aspects of pathology reduction degree and experiment controllability is broken through.

Compounds comprising an amide-linked coumarin scaffold, compositions comprising same, and method of using such compounds and compositions to inhibit tubulin-associated unit (tau) protein aggregation or alpha-synuclein ( α-syn) protein aggregation in a subject having, or at risk for, tau protein aggregation or α-syn protein aggregation, respectively.

The application discloses expression regulation of alpha-synuclein and application thereof. The alpha-synuclein inhibitor is used for preparing a medicine, and the obtained medicine has the effects of preventing and treating anxiety caused by social isolation. Experiments prove that after the alpha-synuclein inhibitor is administered, the anxiety behavior of a model animal in a social isolation environment can be improved, and the alpha-synuclein inhibitor has a treatment effect on anxiety caused by social isolation. The alpha-synuclein inhibitor is selected from the following: 1) an ASO targeting SNCA mRNA coding alpha-synuclein; 2) a small-molecule compound targeting SNCA mRNA coding alpha-synuclein; or 3) an AAV interfering with the expression level of alpha-synuclein in a ventral hippocampal neuron.

An engineered tyrosyl-tRNA synthetase / tRNA pair that co-translationally incorporates O-sulfotyrosine in response to UAG codons in E. coli and mammalian cells is described herein. This platform enables recombinant expression of eukaryotic proteins homogeneously sulfated at chosen sites.

The invention relates to a method for detecting misfolded alpha-synuclein protein in a biological sample to determine the presence of synucleinopathies in an individual. The method provided by the present invention can also be used for differential diagnosis of Lewy fold synucleinopathies from MSA synucleinopathies as well as for monitoring of the disease progression in individuals. Moreover, a kit for detecting misfolded αSyn protein in biological samples is provided.

A novel class of fusion proteins is disclosed that recruits the cell's innate chaperone machinery, specifically the Hsp70-mediated system, to specifically reduce alpha-synuclein-mediated protein aggregation and associated proteopathies.

The disclosure provides peptide compositions and immunotherapy compositions comprising an amyloid-beta (Aβ, Abeta) peptide, a tau peptide, and an alpha-synuclein peptide. The disclosure also provides methods of treating or effecting prophylaxis of Alzheimer's disease or other diseases with beta-amyloid deposition in a subject, including methods of clearing deposits, inhibiting or reducing aggregation of Aβ and tau and an alpha-synuclein, blocking the uptake by neurons, clearing amyloid, and inhibiting propagation of tau seeds and an alpha-synuclein synucleinopathies in a subject having or at risk of developing Alzheimer's disease or other diseases containing tau and amyloid-beta and an alpha-synuclein accumulations. The methods include administering to such patients the compositions comprising an amyloid-beta (Aβ) peptide and a tau peptide and an alpha-synuclein peptide.

A system and method for protein detection are provided, configured to non-invasively identify proteins exhibiting specific structural conformations within a biological target. The system comprises a light source operable to irradiate the target at a predetermined pulse cycle, a sound detection device configured to capture acoustic signals generated via the photoacoustic effect, and an information processing unit that analyzes the detected acoustic signals to determine the presence or accumulation of a target protein. This technique facilitates early-stage detection of disease-associated proteins, such as amyloid-β and misfolded α-synuclein fibrils, without requiring complex imaging modalities or invasive biopsy procedures.

The application provides a longan peptide preparation method, product and application, and relates to the technical field of bioactive peptide processing. The longan peptide preparation method comprises the following steps: grinding longan kernels, adding water, and performing first enzyme hydrolysis to obtain an enzyme hydrolysate; the enzyme hydrolysate is inactivated, the pH value is adjusted to 8-9, stirring is performed at 30-40 DEG C, centrifugation and dialysis are performed, a supernatant is obtained, the pH value of the supernatant is adjusted to 4-6, and centrifugation is performed after standing to obtain longan kernel protein; the longan kernel protein is subjected to second enzyme hydrolysis, then inactivated, filtered, concentrated, and dried to obtain the longan peptide; the first enzyme hydrolysis is enzyme hydrolysis using cellulase, acid protease and glutamine enzyme; and the second enzyme hydrolysis is enzyme hydrolysis using trypsin, papain and carboxypeptidase. The longan peptide prepared by the application can effectively inhibit alpha-glucosidase, and achieve a sugar control effect.

The present disclosure relates to compositions and methods for providing neuroprotection in a subject and for treating neurodegenerative diseases and traumatic brain or spinal cord injury. In embodiments, the present disclosure provides agents that bind to cytoplasmic heteronuclear kernel glyconucleoprotein (hnRNP) in neurons and are capable of inhibiting neuronal cell death.

The application discloses a urine biomarker for ovarian cancer detection and a screening method and application thereof. The urine biomarker is selected from at least one of the following (1)-(5): (1) heterogeneous nuclear ribonucleoprotein A3; (2) polymeric immunoglobulin receptor; (3) small integral membrane protein 24; (4) collagen type V alpha 2 chain; and (5) microtubule-associated protein 2. The urine polypeptide group biomarker of the application has high sensitivity and specificity when used for ovarian cancer detection, and the detection process is simple and non-invasive, which is favorable for improving the early diagnosis rate of ovarian cancer and improving the survival period of ovarian cancer patients.

The present invention relates to a composition for diagnosing Parkinson's disease, comprising a preparation for detecting a protein comprising GLUT3 in combination with one or more substances selected from the group consisting of USP14, alpha-synuclein, and AIMP2, or a gene encoding the protein. When using the composition for diagnosing Parkinson's disease and the diagnostic kit comprising the composition according to the present invention, it is possible to detect or diagnose Parkinson's disease by distinguishing Parkinson's disease patient groups by a simple blood test. Further, the present invention can be used as a pre-diagnosis for determining whether or not neurological examinations or brain image examinations are to be performed in a large hospital by preferentially applying to patients who exhibit premonition symptoms of Parkinson's disease such as anomalies, sleep disorders, and constipation. In addition, the compound can be used as a means for quantifying the treatment effect of Parkinson's disease.

The invention discloses a drying protective agent for nuclear signal cell climbing slide. The drying protective agent comprises the following components: 80 g / L of trehalose, 30 g / L of sucrose, 5% of mannitol by volume fraction, 0.5% of TritonX-100 by volume fraction, 30 g / L of hydroxyethyl starch, 40 g / L of BSA, 40 g / L of sodium carboxymethyl cellulose, 40 g / L of polyvinylpyrrolidone, 10 g / L of cysteine and 5-7 g / L of sodium citrate. In the protective agent, TritonX-100 can pass through a cell membrane to release nucleoprotein, sample or antibody incubation can be directly carried out without permeation in subsequent detection, and other effective components can be loaded into cells to play a good stabilizing and protecting role in the cell drying process, so that morphological variation and damage of the cells are effectively avoided, antigen protein conformation is maintained, and the cell quality is improved. Therefore, the stability of the dried cells is improved.

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.

The invention discloses application of modified small nuclear RNA (Ribonucleic Acid) and a protein complex thereof in enhancing plant photosynthesis. The invention relates to the technical field of biology, and provides a small nuclear RNA (Ribonucleic Acid) of which the nucleotide sequence is SEQ ID NO: 1 or SEQ ID NO: 2. The invention also provides a small nuclear RNA-protein complex composed of the small nuclear RNA and an Sm protein specifically bound with the small nuclear RNA. The small nuclear RNA and the protein complex thereof disclosed by the invention can be specifically combined with mRNA 3 'UTR regions of a plurality of nuclear coding chloroplast protein genes through base complementary pairing, and the expression of the nuclear coding chloroplast protein is enhanced on the translation level, so that the biosynthesis of chloroplast is promoted, and the photosynthetic efficiency of plants is improved.

This invention relates to a mouse model of Parkinson's disease and its applications. The construction method includes the following steps: 1) in mice... Snack An exogenous fragment containing the human SNCA G51D coding sequence was knocked into the region upstream of the gene stop codon via homologous recombination, causing the human SNCA G51D coding sequence to interact with the mouse endogenous gene. Snack The gene forms a bicistronic expression structure, and the coding sequence of the human SNCA G51D is shown in SEQ ID No:1; 2) Positive F0 generation mice are backcrossed with wild-type mice, and genotypes are identified and screened to obtain a stable SNCA G51D endogenous knock-in Parkinson's disease mouse model. The gene editing strategy of the Parkinson's disease mouse model preserves the mouse's... Snack Simultaneous endogenous expression of α-synuclein G51D in the gene can mimic two pathogenic forms, exhibiting high physiological relevance and genetic authenticity.

The present invention provides small molecule drugs and pharmaceutical compositions for the treatment and prevention of diseases related to the formation of certain types of oligomers in a subject. More specifically, the drugs and compositions reduce or prevent the formation of oligomers formed from tau protein, TDP-43, Huntingtin's protein and / or alpha-synuclein. It further provides a method of reducing formation of or disrupting TDP-43, alpha-synuclein, Huntingtin's protein and / or tau protein oligomers in a subject, the method comprising the step of administering to the subject in need thereof a therapeutically effective amount of a pharmaceutical composition.

The application discloses an in-vitro detection method and kit for O-GlcNAc glycosylation modification of alpha-synuclein, and relates to the field of biochemical detection. Y289L The method comprises the following steps: extracting protein in a sample to be detected, adding UDP-GalNAz substrate beta4GalT Y289L The mutant enzyme and the reaction are carried out to obtain a protein system; DBCO-mPEG is added to the protein system, and the reaction product is subjected to electrophoretic separation; and according to an electrophoretogram, the proportion of the protein subjected to glycosylation modification and the molecular weight distribution thereof are calculated. The application marks specific molecular weight "tags" for O-GlcNAc glycosylation proteins, and the glycosylation-modified proteins are recognized by alpha-synuclein specific antibodies to show specific molecular weight sizes; and the alpha-synuclein polymerization states, such as dimers and polymers, subjected to O-GlcNAc glycosylation modification can be determined and quantified according to protein standards.

This invention provides libraries of Botulinum neurotoxin A (BoNT / A) protease variants for stepwise evolution of the enzyme to generate BoNT / A variants that can specifically cleave a desired cleavage site in a target protein. Related methods for performing stepwise evolution of BoNT / A with the BoNT / A variant libraries and simultaneous stepwise evolution of a desired substrate sequence in a target protein are also provided by the disclosure. Additionally provided in the disclosure are specifically evolved BoNT / A variant enzymes and conjugate proteins that specifically degrade intrinsically disordered proteins (IDPs) that are involved in human deceases, e.g., a-Synuclein. Polynucleotide sequences encoding the engineered BoNT / A proteases, expression vectors and related pharmaceutical compositions are also provided in this disclosure. Further encompassed by the invention are therapeutic methods that utilize the engineered BoNT / A enzymes in the treatment of various synucleinopathies.

A method is provided for detecting various isoforms of synuclein protein by detecting the amino acid sequences of synuclein peptides generated by proteolysis of synuclein present in a sample from a subject suspected of suffering from a neurodegenerative disease.

The invention relates to the field of medical detection, in particular to a detection reagent, a detection kit and a detection method for amyloid protein aggregates. The invention provides a seed amplification test method of a pathological alpha-synuclein aggregate, which comprises the following steps: coating or fixing a specific anti-alpha-Syn antibody at the bottom and the side surface of an elisa plate, capturing the pathological alpha-Syn aggregate in a sample by using the specific anti-alpha-Syn antibody, washing off uncombined alpha-Syn or other substances, and detecting the pathological alpha-synuclein aggregate. Various factors interfering amplification in a sample are effectively removed, oscillation-intermittent-oscillation period incubation amplification is carried out in a buffer solution containing an alpha-Syn monomer, pathological alpha-Syn aggregate serving as a seed is adsorbed to an interface of a solid phase and a liquid phase with the maximum shear stress in the initial stage of SAA amplification, the alpha-Syn aggregation efficiency is greatly improved, and the amplification efficiency is improved. The delay time of the initial stage is shortened, so that the amplification time is greatly shortened, and the problems existing in the alpha-Syn-SAA test at present are solved.

Compounds having general formula I, a method for preparing same, a pharmaceutical composition thereof, and use thereof are provided. Specifically, a compound having a structure represented by general formula I, and a racemate, an R-isomer, an S-isomer and a pharmaceutically acceptable salt thereof, or a mixture thereof are provided. The compound promotes transcription factor EB (TFEB) nuclear translocation and lysosome generation, and can be used for preventing, treating, or assisting in treating various diseases related to lysosome dysfunction and biosynthesis insufficiency, especially neurodegenerative diseases caused by the accumulation of intracerebral pathological proteins (e.g., β-amyloid protein and α-synuclein), such as Alzheimer's disease (AD) and Parkinson's disease (PD).