116 results about "Amyloid aggregation" patented technology

A disease characterized by amyloid aggregation in a patient may be prevented or treated by causing antibodies against a peptide component of the amyloid deposit to come into contact with the aggregated or soluble amyloid. In order to decrease the risk of inflammation in such a method, the Fc receptors of the patient are blocked, preferably by administration of an effective amount of IVIg, prior to the procedure of causing the antibodies to come into contact with the amyloid.

To provide a diagnostic drug which binds specifically to an amyloid aggregate and / or an amyloid deposit, to thereby realize imaging and quantification of a disease caused by amyloid aggregation and / or deposition.The invention provides a compound represented by formula (1):(wherein X1 represents an optionally substituted bicyclic heterocyclic group;X2 represents a hydrogen atom, a halogen atom, or a chelate-forming group;ring A represents a benzene ring or a pyridine ring; andring B represents an optionally substituted 5-membered aromatic heterocyclic group which is bonded to the benzene ring or the pyridine ring via a carbon atom of ring B), a salt thereof, a solvate of any of these, or a transition metal coordination compound of any of these, and a diagnostic, preventive, or therapeutic drug containing the same.

A method for increasing the generation of non-amyloidogenic soluble APP comprising activation of protein kinase C (PKC) by administering an effective amount of at least one PKC activator. Also provided is a method for altering conditions associated with amyloid processing in order to enhance an alpha-secretase pathway to generate soluble alpha-amyloid precursor protein (alpha-APP) so as to prevent beta-amyloid aggregation comprising administering an effective amount of a benzolactam.

The invention discloses a method for monitoring beta amyloid protein aggregation process by aggregation-induced emission, belonging to the technical field of biomedical research and clinical detection. With the method, the high affinity between sulfydryl on cysteine and maleimide is utilized to specially combine the beta amyloid protein on an aggregation-induced emission probe. The beta amyloid protein aggregation process is monitored on the basis of aggregation-induced emission enhancement phenomenon. The method has the advantages of high sensitivity, high selectivity, good stability, low manufacture cost and the like and is easy to control. The A beta42 and A beta40 contents can be monitored in a micromole, even a nano-mole level, the detection speed of the method is improved by 15 times if being compared with that of the detection method which utilizes probes, such as ANS (8-aniline-1-naphthalene sulfonic acid) and the like. The beta amyloid protein aggregation process can be qualitatively and quantitatively monitored, the method has a good application prospect if being applied to the pathologic diagnosis of latent patients suffering from senile dementia.

A disease characterized by amyloid aggregation in a patient may be prevented or treated by causing antibodies against a peptide component of the amyloid deposit to come into contact with the aggregated or soluble amyloid. In order to decrease the risk of inflammation in such a method, the Fc receptors of the patient are blocked, preferably by administration of an effective amount of IVIg, prior to the procedure of causing the antibodies to come into contact with the amyloid.

The invention discloses a polypeptide for inhibiting aggregation and toxicity of beta amyloid protein (A beta) or a variant of the polypeptide with polypeptide functions. The polypeptide has a strong binding force with the A beta protein, so that the effective content of a beta structure can be greatly reduced when A beta achieves an aggregation balanced state, the secondary structure of A beta in a solution environment can be changed, the content of the beta structure can be greatly reduced, even the beta structure disappears, the toxicity of A beta to SH-SY5Y cells can be remarkably reduced when the concentration of the polypeptide is extremely low, and generation of A beta-induced active oxygen can be greatly inhibited. Therefore, a feasible method is provided to treatment of Alzheimer disease caused by beta amyloid protein, and thought and reference standard can be provided to discovery of polypeptide pilot compounds for treatment of amyloid protein related diseases.

The invention discloses an application of a guanidino compound represented by formula I or a pharmaceutically acceptable salt of the guanidino compound in the preparation of medicines for treating nervous system degenerative diseases. R in the formula I is hydrogen, a carboxyl group or a -C1~C5 alkyl-carboxyl group. The guanidino compound has a substantial protection effect on hydrogen peroxide induced neonatal rat hippocampal nerve cell injures, has a substantial inhibition effect on in vitro beta-amyloid protein aggregation, and has potential clinic application values.

Disclosed are compounds of the Formula I and their use in a method of inhibiting the aggregation of amyloid proteins and in a method of imaging amyloid deposits.

The invention belongs to the field of microbial medicine, and discloses applications of demethoxyviridin, a steroid compound, in preparing an Amyloid-beta aggregation inhibitor. The Amyloid-beta aggregation inhibitor is used for preparing medicament for treating Alzheimer's disease. The demethoxyviridin is obtained by fermenting and separating Nodulisporium sp. 65-12-7-1.

The present invention relates to spirocyclic acylguanidines and their use as inhibitors of the β-secretase enzyme (BACE1) activity, pharmaceutical compositions containing the same, and methods of using the same as therapeutic agents in the treatment of neurodegenerative disorders, disorders characterized by cognitive decline, cognitive impairment, dementia and diseases characterized by production of β-amyloid aggregates.

The invention relates to the provision of compounds, methods for producing them, and their use for imaging and quantification of aggregates of β-amyloid peptides in vivo. In a preferred aspect of the invention, a tracer is administered to humans and displays enrichment in body parts that are containing aggregates of amyloid peptides. Tracers of the invention can be used for non-invasive depiction and quantification of aggregates of β-amyloid peptides in humans affected with diseases that are characterized in the generation of such aggregates.

The present invention provides a method of treating Alzheimer's disease using a compound of Formula (I). Also provided is a method of inhibiting the aggregation of amyloid proteins using a compound of the Formula (I) and a method of imaging amyloid deposits, as well as new compounds of Formula (I).

A peptide probe that generates fluorescence signals rapidly upon recognition of various Aβ aggregates without significant perturbation of samples. The present peptide probes display an increase in fluorescence signals upon coincubation with Aβ oligomers, but neither monomeric / dimeric species nor fibrils. The detection can occur within an hour or two without any additional sample preparation and incubation steps.

The present invention relates to spirocyclic acylguanidines and their use as inhibitors of the β-secretase enzyme (BACE1) activity, pharmaceutical compositions containing the same, and methods of using the same as therapeutic agents in the treatment of neurodegenerative disorders, disorders characterized by cognitive decline, cognitive impairment, dementia and diseases characterized by production of β-amyloid aggregates.

The invention belongs to the technical field of medicines, health-care products or foods, and provides application of fast green in inhibition of aggregating of beta-amyloid protein to inhibit the medicines, health-care products or foods with aggregating of beta-amyloid protein. The fast green can change the morphology of aggregating, and block and delay the conversion of beta-amyloid protein intofibrous morphology; the process of secondary structure in beta-amyloid protein to beta-folding and converting is delayed; the toxicity to the cells by the beta-amyloid protein aggregation is effectively inhibited.

The invention discloses an application of brazilin to preparation of drug or a health care product for inhibiting aggregation of beta-amyloid proteins. Various experimental means prove that brazilin can inhibit amyloid beta 42 aggregation, can change the appearance of the amyloid beta 42 aggregation, prevents and slows down the conversion of the appearance of the amyloid beta 42 aggregation into the fibrous appearance, slows down the process of converting a secondary structure of the amyloid beta 42 into a beta-sheet structure, decreases the content of the amyloid beta 42 converted into the beta-sheet in the solution, and inhibits the amyloid beta 42 aggregation from producing a toxic effect on cells effectively. Brazilin is considered as a potential new rug or health care product molecule, can inhibit amyloid beta 42 aggregation effectively and the comformational change process of the amyloid beta 42 aggregation, reduces the cytotoxic effect generated during the amyloid beta 42 aggregation process, and is an ideal inhibitor for amyloid beta 42 aggregation.

Amine chelates capable of antioxidant capacity and amyloid disaggregation are shown which may be useful in targeting metal-based oxidative stress in neurodegenerative disorders. Pyclen, a backbone commonly investigated for contrast agent imaging, may be repurposed as an anti-oxidant chelator for disaggregating amyloid. The antioxidant capacity of pyclen is enhanced dramatically via conversion of the pyridine backbone to a pyridol with cellular studies showing superior antioxidant capacity while retaining chelation ability to protect amyloid from metal ions aggregation and also disaggregate amyloid aggregates. Another family of molecules based upon hybrid heterocyclic amine ligands is also presented.

The invention relates to a detection method of amyloid protein. Specifically, the detection method is realized by means of the unique structure and the luminescent characteristic of carbon-based quantum dots serving as fluorescent probes. A novel scheme is provided for aggregation detection of amyloid protein, and interference to a to-be-detected system in a traditional fluorescent detection method is avoided.

The present invention relates to spirocyclic acylguanidines and their use as inhibitors of the β-secretase enzyme (BACE1) activity, pharmaceutical compositions containing the same, and methods of using the same as therapeutic agents in the treatment of neurodegenerative disorders, disorders characterized by cognitive decline, cognitive impairment, dementia and diseases characterized by production of β-amyloid aggregates.

Compounds that modulate the aggregation of amyloidogenic proteins or peptides are disclosed. The modulators of the invention can promote amyloid aggregation or, more preferably, can inhibit natural amyloid aggregation. In a preferred embodiment, the compounds modulate the aggregation of natural β amyloid peptides (β-AP). In a preferred embodiment, the β amyloid modulator compounds of the invention are comprised of an Aβ aggregation core domain and a modifying group coupled thereto such that the compound alters the aggregation or inhibits the neurotoxicity of natural β amyloid peptides when contacted with the peptides. Furthermore, the modulators are capable of altering natural β-AP aggregation when the natural β-APs are in a molar excess amount relative to the modulators. Pharmaceutical compositions comprising the compounds of the invention, and diagnostic and treatment methods for amyloidogenic diseases using the compounds of the invention, are also disclosed.

The invention discloses benzothiazole derivatives represented by general formulas (I)-(II) and pharmaceutically acceptable salts thereof, which have inhibition and developing effects on aggregation and precipitation of amyloid beta-protein. When being used as developers, the benzothiazole derivatives are required to be marked with appropriate radioactive isotopes or contrast agents which are applicable to magnetic resonance detection. The compounds are applied to producing drugs for preventing and treating diseases including Alzheimer's disease, and the developers are applied to aggregates and sediments of amyloid beta-protein.

The present invention is directed to compounds that inhibit amyloid aggregation and methods of treatment there-with.

The invention relates to radiolabeled compounds and their use in methods of imaging amyloid deposits, as well as to methods of their manufacture. The invention also relates to compounds for inhibiting the aggregation of amyloid proteins that form amyloid deposits, methods for delivering therapeutic agents to amyloid deposits, as well as methods of making compounds that inhibit the aggregation of amyloid proteins.

The invention relates to a preparation method of difunctional copolymerized nanoparticle inhibitor and application thereof in inhibition and detoxification of amyloid beta protein aggregation. The preparation method includes: using a connection product GMA-IDA of iminodiacetic acid (IDA) and glycidyl methacrylate (GMA) as a monomer; subjecting the monomer to free radical copolymerization reaction with monomers like N-isopropylaccrylamide (NIPAm) and n-tertbutyl acrylamide (TBAm) to synthesize the difunctional nanoparticle inhibitor having metal chelation ability and protein aggregation inhibiting ability. Average particle diameter of difunctional copolymerized nanoparticles synthesized by the method is 80-120nm. Metal ion chelation capacity of the nanoparticles synthesized by the method is higher than 700umol / g, and the nanoparticles can chelate metal ions in environment and inhibit fibrosis aggregation of Abeta42 and are a potential new drug raw material for treating Alzheimer's disease.

The invention relates to radiolabeled compounds and their use in methods of imaging amyloid deposits, as well as to methods of their manufacture. The invention also relates to compounds for inhibiting the aggregation of amyloid proteins that form amyloid deposits, methods for delivering therapeutic agents to amyloid deposits, as well as methods of making compounds that inhibit the aggregation of amyloid proteins.

The invention relates to a serum albumin with a metal chelating function as well as a preparation method and an application in inhibition for the aggregation of beta-amyloid proteins. The serum albumin with the metal chelating function is obtained through modifying 1,4-butanediol diglycidyl ether on an amino group on the surface of a serum albumin at first, and then modifying a metal chelating agent iminodiacetic acid on an epoxy group of 1,4-butanediol diglycidyl ether, and the average modification number of iminodiacetic acid on each serum albumin ranges from 2 to 40. According to the serum albumin with the metal chelating function, which is disclosed by the invention, the chelating capacity of the serum albumin for metal ions is improved, and then the self-aggregation of the beta-amyloid proteins and an aggregation process of the beta-amyloid proteins under the induction of the metal ions are inhibited, and the cytotoxicity of beta-amyloid protein aggregates is reduced. The serum albumin with the metal chelating function is used for a medicine for treating the diseases related to beta-amyloid protein aggregation. The medicine is used for treating and slowing down Alzheimer disease and other diseases.

Compounds useful in the treatment of disorders characterized by deposits of amyloid aggregates are herein described together with pharmaceutical compounds containing the same. In particular the compounds of the present invention are those having the Formula (I) as reported below, where the radicals have the meaning indicated in the description.

Compounds that modulate the aggregation of amyloidogenic proteins or peptides are disclosed. The modulators of the invention can promote amyloid aggregation or, more preferably, can inhibit natural amyloid aggregation. In a preferred embodiment, the compounds modulate the aggregation of natural β amyloid peptides (β-AP). In a preferred embodiment, the β amyloid modulator compounds of the invention are comprised of an Aβ aggregation core domain and a modifying group coupled thereto such that the compound alters the aggregation or inhibits the neurotoxicity of natural β amyloid peptides when contacted with the peptides. Furthermore, the modulators are capable of altering natural β-AP aggregation when the natural β-APs are in a molar excess amount relative to the modulators. Pharmaceutical compositions comprising the compounds of the invention, and diagnostic and treatment methods for amyloidogenic diseases using the compounds of the invention, are also disclosed.