25 results about "Amyloid aggregation" patented technology

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.

In nerve diseases, cell dysfunction due to amyloid aggregate accumulation in nerve cells has attracted attention, but dysfunction of nerve axons responsible for neurotransmission is also considered to be one of the causes. However, no therapeutic agent that focuses on the repair and maintenance of nerve axons has been found. An object of the present invention is to provide a therapeutic agent that activates oligodendrocytes having a function of preserving nerve axons.SOLUTION: Transcriptome analysis with a psychotropic drug is carried out using an oligodendrocyte marker as an indicator, and it is found that the combined use of DPZ and NFN characteristically increases the expression of a transcriptional factor OLIG1 inducing the differentiation-maturation of the oligodendrocyte. Moreover, the drug concentration at this time was much lower than the expected clinical dose. The combined use of NFN and DPZ was observed to improve spatial memory in the mouse Y-maze test. The combination of NFN and DPZ can provide a novel treatment for cognitive and memory functions associated with neurological disorders.SELECTED DRAWING: None

One aspect relates to a composition for preventing or treating degenerative brain diseases comprising induced pluripotent stem cell-derived mitochondria. According to one aspect, the mitochondria derived from induced pluripotent stem cells were confirmed to exhibit excellent effects in removing reactive oxygen species and in reducing expression of inflammatory cytokines, thereby providing anti-inflammatory effects superior to those of mitochondria derived from other cells. When the mitochondria are treated to damaged nerve cells, recovery and regeneration effects can be confirmed on nerve cells, and as a result of administering the mitochondria to elderly mice, it was also confirmed that the mitochondria have an anti-aging effect. Accordingly, the pharmaceutical composition comprising induced pluripotent stem cell-derived mitochondria according to one aspect of the present invention can be applied in various fields for the prevention or treatment of degenerative brain diseases, particularly bone diseases caused by aging or beta amyloid aggregation.

The invention discloses application of a theaflavin compound in preparation of a medicine for inhibiting beta amyloid peptide aggregation, and belongs to the technical field of biological medicine. Multi-dimensional experiments prove that the galloyl group in the theaflavin compound can significantly inhibit the formation of Abeta42 amyloid fibers, reduce the generation of toxic oligomers and reconstruct formed oligomers by increasing binding sites with Abeta42 polypeptide and enhancing polar interaction and hydrophobic interaction. The TF3 (containing two galloyl groups) has the optimal anti-Abeta 42 polypeptide aggregation activity, a precise target spot is provided for design of an Abeta amyloid aggregation inhibitor taking the galloyl groups as a core structure, and an experimental basis is provided for application of a natural polyphenol compound in preparation of a medicine for preventing or treating Alzheimer's 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.

This invention discloses a composite anticoagulant coating, its preparation method, and its applications, belonging to the field of biomedical technology. This invention provides a novel composite anticoagulant coating. Through the following innovative design: using multi-thiol proteins (bovine serum albumin, lysozyme, etc.) as coating substrates, in-situ bio-orthogonal multiple grafting is performed on their thiol groups and amino groups to achieve multifunctionality of anticoagulation, anti-inflammation, and antibacterial properties; through the amyloid aggregation of proteins, a strong target substrate is formed and anchored, resisting blood flow impact and improving coating stability. This invention, through bio-orthogonal design, modifies the thiol groups and amino groups of the coating proteins separately to achieve non-conflicting multifunctionality. Specifically, by modifying the disulfide bonds (-S-S-) and branched amino groups (-NH2) of the proteins, dual active sites of -SH and -GA are constructed for grafting modification, allowing the grafted substances to achieve their multifunctionality of anticoagulation, anti-inflammation, and antibacterial properties without interference.

Aspects of the present invention disclose compounds that modulate the aggregation of amyloidogenic proteins or peptides. In some aspects, disclosed compounds modulate the aggregation of disease-associated proteins and natural β-amyloid peptides. In a preferred embodiment, the compounds can inhibit natural amyloid aggregation. Pharmaceutical compositions comprising the compounds of the embodiments, and diagnostic and treatment methods for diseases (e.g., amyloidogenic diseases) using the compounds, are also disclosed. In addition, there is provided an integrated bacterial platform for the discovery of rescuers of disease-associated protein misfolding.

The invention discloses radiopharmaceutical composition of Fluorine-18 (F18) labelled styrylpyridine compounds, for use as a medicament for the treatment or diagnosis of a disease or condition associated with build-up of amyloid-β (Aβ) aggregates. The invention further relates to polymorphic forms of precursors of F18 Florbetapir and their use for preparing F18 Florbetapir.

A drug that inhibits aggregation of amyloid-β, which causes Alzheimer's disease and the like. The amyloid-βaggregation inhibitor is characterized by containing at least one of a peptide having an amino acid sequence of SEQ ID NO: 1 (GSGNR) or a peptide having an amino acid sequence of SEQ ID NO: 2 (GSGFK). A pharmaceutical composition for an amyloid-βaggregation disease is characterized by containing at least one of a peptide having an amino acid sequence of SEQ ID NO: 1 (GSGNR), and a peptide having an amino acid sequence of SEQ ID NO: 2 (GSGFK).

The invention discloses radiopharmaceutical composition of Fluorine-18 (F18) labelled styrylpyridine compounds, preferably F18 Florbetapir, free of undesirable nitrosamine drug substance related impurities (NDSRI) and other undesirable impurities. The prepared radiopharmaceutical composition is used as a medicament for the treatment or diagnosis of a disease or condition associated with build-up of amyloid-β (Aβ) aggregates.

The invention relates to the field of drug carrier design, in particular to a traditional Chinese medicine nano delivery system with a targeted A beta protein aggregation inhibition function as well as a preparation method and application of the traditional Chinese medicine nano delivery system. The traditional Chinese medicine nano-delivery system is a traditional Chinese medicine nano-carrier which is based on polypeptide A beta 16-21-r9 as shown in the amino acid sequence SEQ ID NO.1 and has the cell barrier penetrating and amyloid protein capturing capacity, and beta amyloid protein aggregation activity can be regulated in a targeted mode through the carrier. According to the traditional Chinese medicine nano delivery system prepared by the preparation method disclosed by the invention, the efficient delivery of a drug carrier can be realized, the blood brain barrier can be quickly penetrated, and the A beta protein can be accurately targeted.

The present invention relates to peptides, in particular of amyloid inhibitory peptides, and to pharmaceutical compositions comprising such peptides, for use in methods of treating or preventing or delaying the onset of synucleinopathies, in particular of Parkinson's disease (PD) or dementia with Lewy bodies, and their comorbidities, in particular PD / type 2 diabetes (T2D) and PD / Alzheimer's disease (AD). Furthermore, the present invention relates to such peptides, in particular such amyloid inhibitory peptides, for use in methods of diagnosing such synucleinopathies and related comorbidities. Furthermore, the present invention also relates to a kit for the in-vitro or in-vivo detection and, optionally, quantification of amyloidogenic polypeptides, amyloid fibrils or amyloid aggregates, and / or for the diagnosis of synucleinopathies and related comorbidities, in particular PD / type 2 diabetes (T2D) and PD / Alzheimer's disease (AD), in a patient.

Provided herein a method for treating or preventing a protein misfolding and deposition disease in a subject, by administering to the subject a low dose amount of compound (1). Provided herein is also a method for reversing or preventing the toxic effect of the misfolded and aggregated protein amyloid beta, by using compound (1) in a relative undersupply (reversed stoichiometric ratio) to achieve stronger detoxifying effects. Also provided dosages and administration thereof.

Aspects of the present invention disclose compounds that modulate the aggregation of amyloidogenic proteins or peptides. In some aspects, disclosed compounds modulate the aggregation of disease-associated proteins and natural β-amyloid peptides. In a preferred embodiment, the compounds can inhibit natural amyloid aggregation. Pharmaceutical compositions comprising the compounds of the embodiments, and diagnostic and treatment methods for diseases (e.g., amyloidogenic diseases) using the compounds, are also disclosed. In addition, there is provided an integrated bacterial platform for the discovery of rescuers of disease-associated protein misfolding.

The invention discloses to radiopharmaceutical composition of Fluorine-18 (F18) labelled styrylpyridine compounds, preferably F18 Florbetapir, that are free of undesirable nitrosamine drug substance related impurities (NDSRI) and other undesirable nitrosamine impurities. The disclosed radiopharmaceutical composition is used as a medicament for the treatment or diagnosis of a disease or condition associated with build-up of amyloid-β (Aβ) aggregates.

The present disclosure belongs to the field of fluorescent probes, and provides a fluorescent ratio probe and a development method and application thereof. The fluorescent ratio probe is 4-(4-dimethylaminostyryl) quinoline, referred to as QD, which is used for imaging and detection of beta-amyloid aggregates (referred to as Aβs) and monitoring of pH changes of the environment where the Aβs are located. The development method of the probe is also disclosed, and the application of the probe in preparation of a product for diagnosing the disease progression of Alzheimer's disease, which comprises the probe. The present disclosure provides a bifunctional fluorescent ratio probe QD which can light up Aβs and monitor the surrounding pH microenvironment, and has the characteristics of high affinity, good repeatability and simple operation. The QD has dual-color fluorescence when combined with Aβs, and the fluorescence ratio changes with the pH of the environment where the Aβs are located, so that the QD can be used to label Aβs in vivo and in vitro and display the pH microenvironment around the Aβs.

The invention discloses an efficient and safe A beta 42 variant antibacterial peptide with esterase activity and application thereof. A natural amyloid peptide A beta 42 sequence is used as a basis for modification, an aggregation segment is selected, a sequence (six continuous Arg capable of inhibiting amyloid aggregation and providing positive charges) with a specific effect is added to an N terminal, a C terminal is connected with esterase catalysis triad amino acids S, H and D through two glycines (G) respectively, and mixing is carried out according to a molar ratio of 1: 1: 1. The oligopeptide is obtained through artificial synthesis, and a series of physicochemical properties such as antibacterial activity and the like of the obtained hybrid peptide are determined to evaluate whether the hybrid peptide is AMP or not and the activity intensity of the hybrid peptide. Based on a natural amyloid peptide sequence, rational design and transformation are carried out, verification is carried out through a series of experiments, the novel antibacterial peptide can be efficiently and rapidly researched and developed, and the problems that at the present stage, antibacterial peptide obtaining ways are few, the difficulty is large, and the effect is poor are solved.

The present application relates to the technical field of medicine, and more particularly to a polypeptide for inhibiting and / or eliminating beta-amyloid aggregation and application thereof. The present application first develops a functional active polypeptide ANI-1 which can act on diseases caused by beta-amyloid aggregation and deposition such as Alzheimer's disease from multiple targets, so as to effectively prevent and treat the diseases. The polypeptide ANI-1 of the present application has the functions of eliminating A beta aggregation, delaying behavioral decline caused by beta-amyloid toxicity (anti-paralysis, promoting movement), inhibiting neurogenic inflammation related to beta-amyloid deposition and enhancing antioxidant defense, has better overall efficacy and neuroprotective potential, and can provide a new idea for developing a multi-target drug for diseases caused by beta-amyloid aggregation and deposition such as Alzheimer's disease.

The present invention provides synthetic peptides, pharmaceutical compositions containing synthetic peptides, and the use of synthetic peptides for the treatment of amyloidosis. [Solution] The synthetic peptide of the present invention has the effect of preventing the formation of β-amyloid aggregation and preventing the folding and aggregation of β-amyloid (amyloidβ, Aβ), tau protein, α-synuclein (α-synuclein, α-Syn), islet amyloid polypeptide (IAPP), or transthyretin (TTR), thereby treating amyloidosis.

The invention belongs to the technical field of biological medicines, and particularly relates to a substituted coumarin-benzoxazole derivative as well as a preparation method and application thereof. The derivative has a structure shown in a formula (I) or (II), R1 is selected from hydrogen, methyl, chlorine and formyloxyethyl, R2 is selected from hydrogen, methyl, trifluoromethyl and a benzene ring, and n is a positive integer ranging from 2 to 5. The preparation is realized through two-step substitution reaction, raw materials are cheap, the process is simple and convenient, and the method is suitable for industrial production. The derivative has remarkable multi-target activity, can inhibit monoamine oxidase-B and beta-amyloid protein aggregation and butyrylcholine esterase at the same time, has a good antioxidant effect, can effectively improve pathological injuries related to neurodegenerative diseases, and is low in biotoxicity and high in safety. The invention can be used for preparing drugs for treating Alzheimer's disease, Parkinson's disease and other diseases, provides a new efficient candidate molecule for the treatment of related diseases, and has important medical research value and market application prospect.

The present disclosure provides a method for preventing formation of amyloid β aggregation and a method for treating amyloidosis by using a synthetic peptide. The synthetic peptide of the present disclosure achieves the effect of preventing formation of amyloid β aggregation and treating amyloidosis through various efficacy experiments.

A method of using brincidofovir (BCV) or a pharmaceutical composition thereof to suppress amyloid β aggregation, neuronal cell degeneration, or phosphorylation of Tau is described.

This invention discloses a class of piperidine alkyl dihydroxyphthalide compounds (I) and their pharmaceutically acceptable salts, their preparation methods, pharmaceutical compositions, and their use in the preparation of medicaments for treating and / or preventing diseases by means of anti-oxidative stress, inhibition of amyloid aggregation, metal ion complexation, or anti-neuroinflammatory effects, including but not limited to vascular dementia, Alzheimer's disease, frontotemporal dementia, Prion's disease, Lewy body dementia, Parkinson's disease, Huntington's disease, HIV-related dementia, multiple sclerosis, amyotrophic lateral sclerosis, neuropathic pain, ischemic stroke, hemorrhagic stroke, and neurological damage caused by traumatic brain injury;

The invention provides a functionalized nano magnetic sphere, a preparation method thereof and an application of the functionalized nano magnetic sphere in detection of A beta protein aggregate in body fluid, is suitable for detection of beta-amyloid protein aggregate in human cerebrospinal fluid or serum, and belongs to the technical field of medical in-vitro diagnosis. According to the invention, Fe3O4 (at) SiO2 is adopted as a carrier material, and an 8c fluorescent probe is grafted on the nano magnetic sphere through a chemical modification method, so that efficient capture of the A beta protein aggregate by the functionalized nano magnetic sphere is realized. The functionalized nano magnetic sphere prepared by the invention can realize the detection of beta-amyloid protein aggregate in body fluid by enriching and separating trace A beta protein aggregate in a cerebrospinal fluid / serum sample.

This invention discloses a method for regulating β-amyloid protein aggregation based on circularly polarized light and its application. The method includes electrostatically binding an amino-modified upconversion luminescent nanoparticle to a SiO2-coated chiral optically active nanostructure to obtain an upconversion chiral nanomaterial; coating the surface of the upconversion chiral nanomaterial with a biocompatible coating and a brain-targeting ligand, then mixing it with β-amyloid protein, and targeting the region with 5–100 mW / cm² light. 2 Irradiation with an 800–1400 nm laser for 15–30 min excites upconversion chiral nanomaterials to emit circularly polarized light. This circularly polarized light inhibits the aggregation of β-amyloid protein by interfering with the formation of its β-sheet conformation. This invention utilizes circularly polarized light (CPL) to induce changes in key protein site interactions, thereby altering the conformation of protein aggregation. This process is reversible and highly spatially selective. Animal experiments have verified that this method can effectively block Aβ aggregation and improve cognitive function.