42 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.

A group of novel 9H-fluorene derivatives suitable for the preparation of active substances for the treatment of Alzheimer's disease, in particular as multifunctional inhibitors of the BuChE and BACE1 enzymes and beta-amyloid aggregation.

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

The invention discloses an amide alkyl thiol ester compound (I) as well as a preparation method and a pharmaceutical composition thereof, and application of the amide alkyl thiol ester compound in preparation of drugs for treating and / or preventing diseases by resisting oxidative stress, inhibiting amyloid protein aggregation and resisting neuroinflammation. Comprising but not limited to vascular dementia, Alzheimer's disease, frontotemporal dementia, Prion disease, dementia with Lewy bodies, Parkinson's disease, Huntington's disease, HIV-related dementia, multiple sclerosis, amyotrophic lateral sclerosis, neuropathic pain, cerebral arterial thrombosis, hemorrhagic stroke, nerve injury caused by cerebral trauma and other diseases; # imgabs0 #

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 present invention relates to the use of scyllo-inositol alone or in combination with other active ingredients, including the flavone apigenin, to support cognitive health in subjects taking the product or combination product. The present invention relates to compositions comprising scyllo-inositol alone or in combination with other agents, including, but not limited to, flavones or other substances that prevent the upregulation or downregulation of aquaporin 4 channels. The compositions, including oral dosage forms such as tablets or capsules, are provided to subjects, including humans or other mammals such as dogs or cats, or other animals, in need of cognitive improvement. The combination product(s) degrade amyloid-β aggregates and promote the clearance of amyloid-β fibrils from the glymphatic system.

Aggregation-induced emission luminogens useful for imaging β-amyloid peptide and aggregates thereof, pharmaceutical compositions comprising the same, and methods of use and preparation thereof.

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).

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 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.

Aggregation-induced emission molecules for imaging of beta-amyloid protein, and inhibiting aggregation of beta-amyloid protein, use and methods of preparation of probes comprising the aggregation-induced emission molecules and derivatives thereof.

The invention relates to application of vinca in preparation of a beta-amyloid protein aggregation inhibitor and an anti-Alzheimer disease preparation, and belongs to the technical field of biological medicines. According to the invention, experiments show that Venoclara can effectively inhibit beta-amyloid protein (A beta) aggregation, change the morphology of beta-amyloid protein aggregation, and prevent and slow down the transformation of beta-amyloid protein to fibrous morphology; furthermore, the invention also finds that the Venoclara can effectively inhibit the cytotoxicity induced by aggregates formed in the beta-amyloid protein aggregation process, and meanwhile, the Venoclara does not cause oxidative damage to cells and has good biological safety when being independently used. The invention provides an inhibitor capable of effectively inhibiting beta-amyloid protein aggregation for the prior art, and provides a new drug resource for research and development of drugs for treating amyloid protein related diseases (such as Alzheimer's disease, cerebral amyloid angiopathy and the like).

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 is applicable to the field of medicines, and particularly relates to a rhizoma cimicifugae-containing traditional Chinese medicine composition for treating Alzheimer's disease, which comprises the following components in parts by weight: 5-15 parts of rhizoma cimicifugae, 8-12 parts of ginseng, 10-15 parts of astragalus membranaceus, 6-10 parts of salvia miltiorrhiza, 4-8 parts of rhizoma acori graminei, 3-6 parts of polygala tenuifolia, 5-8 parts of spina date seed, 10-15 parts of poria cocos, 6-10 parts of radix ophiopogonis, 12-18 parts of oyster, 8-12 parts of concha haliotidis and 4-8 parts of gastrodia elata. The cimicifugae foetidae-containing traditional Chinese medicine composition for treating the Alzheimer's disease has the beneficial effects that the cognitive function is improved: the salvia miltiorrhiza, the rhizoma acori graminei and the polygala tenuifolia can promote cerebral blood perfusion, enhance synaptic plasticity and inhibit neuronal apoptosis; the rhizoma cimicifugae and the radix astragali are combined to improve brain microcirculation and reduce beta-amyloid protein aggregation, so that the learning and memory ability is remarkably improved.

The invention discloses a method for regulating and controlling beta-amyloid protein aggregation based on circularly polarized light and application of the method, and the method comprises the following steps: adding amino-modified up-conversion luminescent nanoparticles into a SiO2-coated chiral optical activity nanostructure for electrostatic binding to obtain an up-conversion chiral nano functional material; the method comprises the following steps: coating the surface of an upconversion chiral nano functional material with a biocompatible coating and a brain-targeting ligand, mixing the upconversion chiral nano functional material with beta-amyloid protein, applying 800-1400 nm laser irradiation to a targeting region at 5-100 mW / cm < 2 > for 15-30 minutes, exciting the upconversion chiral nano functional material to emit circularly polarized light, and forming the circularly polarized light by interfering beta-folded conformation of the beta-amyloid protein, therefore, the aggregation of the beta-amyloid protein is inhibited. Circularly polarized light (CPL) is utilized to induce interaction change of protein key sites, so that conformation of protein aggregation is changed, and the process has reversibility and high spatial selectivity; animal experiments prove that the method can effectively block Abeta aggregation and improve the cognitive function.

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 relates to a health functional food, food or therapeutic pharmaceutical composition for preventing or improving dementia and cognitive function decline, wherein a complex of Pinus densiflora extract and Alpinia officinarum extract is included as an active ingredient, and a preparation method thereof. The complex provided by the present invention is found to have not only excellent acetylcholinesterase inhibitory activity and nitric oxide production inhibitory activity, but also an activity of improving cognitive function decline induced by beta-amyloid administration in an animal model, and thus can be used as a health functional food and a drug for preventing, improving or treating dementia and cognitive function decline.

p53 amyloid-binding composition, method, and kit thereof are disclosed in various embodiments herein. In one embodiment, the p53 amyloid-binding composition is used for the detection and localization of p53 amyloid aggregates and co-aggregates in cancer cells or tissues. The embodiments herein also disclose a method for identifying and differentiating histopathological grades of cancer using the p53 amyloid-binding composition. The method, according to embodiments herein, is a low-cost, efficient, sensitive, and versatile method of staining for the accurate indication of p53 amyloids in cancer cells or tissues, facilitating early detection and accurate assessment of cancer progression. Embodiments herein further disclose a kit for the identification and differentiation of oral and stomach cancers and grades thereof.

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.