282 results about "Nuclear protein" patented technology

Provided herein are methods of cell-free protein synthesis, optimised cell-free protein synthesis (CFPS) reagents for the expression of eukaryotic proteins and methods for optimising CFPS reagents to increase protein expression yields for mammalian proteins and subsequent expression in cells. The methods are applicable to protein expression on a microfluidic device having hydrophobic surfaces by merging droplets on the device in order to screen a selection of expression compositions in parallel and then identify the optimum conditions for producing the stable folded protein in a cell-based system.

The invention discloses an early diagnosis and early screening kit for joint detection of Parkinson's disease and application of the kit, and relates to the technical field of medical treatment. The kit is used for combined detection of three proteins, namely alpha synuclein (alpha-Syn), tyrosine 3-monooxygenase / tryptophan 5-monooxygenase activated protein zeta (YWHAZ) and myosin light chain 6 (Myl6), immunochromatography, chemiluminescence and other methods and a double-antibody sandwich method are adopted, the diagnosis efficiency of the YWHAZ protein is prominent, the AUC reaches 0.96, and the detection sensitivity is high. The AUC of Myl6 is 0.92, the AUC of alpha-Syn is 0.82, the joint detection AUC is up to 0.98, the kit is newly added with a time-resolved fluorescence immunochromatography technology, low-background and high-sensitivity detection is realized through a lanthanide-labeled antibody, the change of related protein expression level can be detected in the early stage of Parkinson's disease, early screening and diagnosis are realized, and the kit has the advantages of high specificity, joint detection up to 95%, high sensitivity, high sensitivity and the like. The joint detection reaches 96%, the operation is simple and convenient, and the sample requirement is low.

Provided herein are compositions that include at least two different nucleic acid vectors, where each of the at least two different vectors includes a coding sequence that encodes a different portion of a stereocilin protein, and the use of these compositions to treat non-syndromic sensorineural hearing loss in a subject.

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 present specification provides a monoclonal antibody that specifically binds aggregated, non-phosphorylated α-synuclein and a hybridoma producing it. Also disclosed are methods of generating antibodies that specifically binds aggregated, non-phosphorylated α-synuclein and uses thereof. Uses of anti-α-synuclein antibody in detection and diagnostic assays, and for prophylaxis or therapy of α-synuclein-associated neurodegenerative diseases, are also disclosed.

The invention relates to the technical field of protein purification, in particular to a purification method of label-free A53T mutant alpha-synuclein. The purification method disclosed by the invention is a purification method which is more efficient and economical and can maintain protein functions, 20mg of protein can be obtained by inducing 1L of bacterial liquid for 4 hours through IPTG, and the method can improve the overall effect and experimental accuracy of preparation of the label-free A53T alpha mutant-synuclein monomer.

The invention discloses a diagnostic marker for Parkinson's disease, application of the diagnostic marker and a heteropolymer detection method, and relates to the technical field of biology. The diagnostic marker is a protein heterozygous aggregate in a brain-derived exosome, and the protein heterozygous aggregate comprises alpha-synuclein and amylin. The invention also provides application of a reagent for detecting the diagnostic marker in preparation of a diagnostic product for Parkinson's disease. According to the present invention, the research results show that the important biomarker protein aggregate in the Parkinson's disease diagnosis is not the aggregate simply formed by polymerizing the alpha-Synuclein (aS) protein, but is doped with the other easily aggregated protein-amylin (Amylin); a heteropolymer composed of aS and Amylin is adopted as a biomarker, and the diagnosis efficiency on the Parkinson's disease can be effectively improved.

To provide novel monoclonal anti-α-synuclein antibodies.SOLUTION: Disclosed is an antibody that can bind to the toxic α-synuclein fragment 1 to 119 / 122 and neutralize this truncated form of α-synuclein. The antibody can be used to treat synucleinopathies such as Parkinson's disease (including idiopathic and hereditary Parkinson's disease), diffuse Lewy body disease (DLBD), Lewy body variant Alzheimer's disease (LBV), combined Alzheimer's and Parkinson's disease, pure autonomic failure, and multiple system atrophy.SELECTED DRAWING: None

The invention belongs to the technical field of biology, and particularly relates to a Parkinson's disease diagnosis kit based on a peripheral red blood cell alpha-synuclein RT-QuIC technology and application of the Parkinson's disease diagnosis kit. The Parkinson's disease diagnostic kit based on the peripheral red blood cell alpha-synuclein RT-QuIC technology comprises a substrate protein, a reaction reagent, a negative reference substance and a positive reference substance, and a sample is selected from red blood cells in blood. The RT-QuIC technology is applied to diagnosis of neurodegenerative diseases, particularly, the sowing activity of pathological alpha-Syn protein is detected in blood red blood cell samples of PD patients of Chinese population for the first time, and the kit has extremely high sensitivity and specificity and provides important reference value for diagnosis and screening of PD. The invention provides a rapid, efficient and accurate diagnostic kit for diagnosis of Parkinson's disease, the kit can be used for accurately detecting Parkinson's disease patients and healthy control, and powerful technical support is provided for clinical diagnosis of the Parkinson's disease patients.

The invention belongs to the field of biological medicine, and particularly relates to application of phosphorylated Parkin protein in preparation of a medicine for treating neurodegenerative diseases carrying pathological alpha-synuclein aggregate characteristics. According to the application, research finds that the Parkin protein and the PINK1 protein have obviously different expression modes in a monkey brain in a physiological state, but the phosphorylation level of the Parkin depends on the expression of the PINK1 protein. Subsequently, it is further found that Parkin phosphorylation expression reduction and obvious aggregation of toxic pS129-alpha-syn occur in both the normal senescent monkey brain and the brain of a sporadic PD patient, and further, it is found through overexpression of wild Parkin that the S65 site phosphorylated Parkin can reduce accumulation of pS129-alpha-syn in the monkey brain, so that the accumulation of pS129-alpha-syn in the monkey brain can be reduced, and the accumulation of pS129-alpha-syn in the monkey brain can be reduced. And the mutant Parkin, which cannot be phosphorylated by PINK1, cannot reduce the aggregation of toxic pS129-alpha-syn. Therefore, the phosphorylated Parkin protein provided by the invention can be used for preparing medicines for treating neurodegenerative diseases carrying pathological alpha-synuclein aggregate characteristics.

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 a cell-penetrating peptide and its derivatives to inhibit α-synuclein fibrillation. The present invention specifically relates to a peptide-based inhibitor of Parkinson's Disease. The present invention discloses the identification of the peptides permeable to blood brain barrier for inhibition. α-synuclein fibril formation is observed in the presence of peptides as indicated by SEQ. ID-7, SEQ. ID-8 wherein the SEQ. ID-7, SEQ. ID-8 are truncated versions of SEQ. ID-4 having the homology of 83% and 75% respectively. It provides a peptide having an amino acid sequence of Formula 1. The present invention also provides a pharmaceutical composition comprising a peptide of Formula 1 along with the pharmaceutically acceptable excipient(s) having inhibitory activity against β-sheet polymerisation of amyloidogenic proteins. The analysis showed that peptides corresponding to SEQ. ID-7, SEQ. ID-8 are better inhibitors than SEQ. ID-4 against α-synuclein fibrillation.

The present invention relates to anti-alpha-synuclein antibodies, and uses thereof for treating diseases such as Parkinson's disease.

The invention discloses a saccharomyces cerevisiae engineering bacterium for producing heme-binding protein as well as a construction method and application of the saccharomyces cerevisiae engineering bacterium. The construction method comprises the following steps: (1) by taking Saccharomyces cerevisiae CEN.PK2-1C as an original strain, optimizing a metabolic pathway, enhancing the supply of cytoplasm alpha-ketoglutaric acid (alpha-KG) and succinyl coenzyme A, and realizing the efficient accumulation of 5-aminolevulinic acid (ALA); (2) regulating and controlling the heme synthesis gene cluster in a time-sharing manner, and cooperatively expressing heme binding protein, so as to improve the assembly efficiency of heme (Heme); and (3) a secretion system is optimized, the secretion bottleneck of eukaryotic protein is broken through, and transmembrane transport and extracellular accumulation of the heme-binding protein are realized. Through the transformation of the combination strategy, an engineering strain for efficiently producing the heme-binding protein is obtained, and the yield of the bean hemoglobin in the saccharomyces cerevisiae is remarkably improved. Under the fermentation condition of a 5L fermentation tank, the secretory expression quantity of the bean hemoglobin reaches 286.6 mg / L.

This disclosure provides recombinant DNA mol-encoding fusion proteins that are able to regulate expression of alpha-synuclein. Also provided are various compositions comprising the recombinant DNA molecules, as well as associated methods of use. The recombinant DNA molecules and associated methods are useful for the treatment of subjects having disorders caused by excess expression or intracellular accumulation of alpha-synuclein, including Parkinson's disease.

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 invention relates to methods of treating early multiple system atrophy (MSA) or MSA-C using anti-alpha synuclein antibodies, such as Amlenetug.

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.

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

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.

The present invention relates to proteins, particularly antibodies such as anti-CD20 / anti-CD3 bispecific antibodies and anti α-synuclein antibodies, having monogalactosylated (Gi) and digalactosylated (G2) glycans. More particular, the present invention relates to galactosylation engineering to generate proteins with improved therapeutic properties, including proteins with increased titer. Further, the invention relates to a cell culture medium and a mammalian cell as well as methods using said cell culture medium and said mammalian cell for producing said proteins. Moreover, the present invention relates to the use of said antibodies as a medicament such as for the treatment of cancer, particularly cancer associated with B-cells, or Parkinson's disease.

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 disclosure pertains to conformational epitopes in alpha-synuclein, antibodies thereto and methods of making and using immunogens and antibodies specific thereto. In particular antibodies raised to cyclic compounds comprising at least 3 amino acids of EKTKEQ (SEQ ID NO: 1) selectively recognize misfolded oligomeric alpha-synuclein and are able to inhibit alpha-synuclein propagation and toxicity.

The present invention relates to a gene therapy for treating synucleinopathies. The present invention provides a novel α-Syn peptide variant and inhibits the formation of amyloid fibrils and degrades α-Syn aggregates, thereby exhibiting excellent preventive, ameliorative, and therapeutic effects on synucleinopathies.