43 results about "Fibril formation" patented technology

The present invention relates to preventives or remedies for Alzheimer's disease, or to amyloid protein fibril-formation inhibitors, which include as an active ingredient a compound of general formula (I) below or a pharmacologically permitted salt thereof; and also to nitrogen-containing heteroaryl derivatives having specific substituents, or pharmacologically permitted salts thereof, which are valuable as preventives or remedies for Alzheimer's disease, or as amyloid protein fibril-formation inhibitors: (where, R1 and R2 are H or alkyl; Z1 and Z2 are H, alkyl, alkoxy, haloalkyl or halogeno; Z3 is alkoxy, SH, alkylthio, NH2, mono- or di-alkylamino, OH or halogeno; Z4 and Z5 are H or halogeno; and A is 4,6-pyrimidine-1,3-diyl, 1,3,5-triazine-2,6-diyl, etc).

It is intended to provide an antibody efficacious in diagnosing, preventing or treating Alzheimer's disease, DNA encoding the antibody, a method of screening a drug and drugs. The amino acid sequence and the gene sequence of the variable region of an antibody, which specifically recognizes a GM1 ganglioside-bound amyloid β-protein occurring in the early stage of β-amyloid fibril formation, are determined. Based on the data of the amino acid sequence and the gene sequence thus obtained, an antibody is designed.

Compositions of and methods for formulating and delivering peptide, polypeptide and protein therapeutic agent formulations having enhanced physical stability, and wherein fibril formation is minimized and / or controlled, to yield a consistent and predictable composition viscosity. The compositions of and methods for formulating and delivering peptide, polypeptide and protein therapeutic agents of the present invention further facilitate their incorporation into a biocompatible coating which can be employed to coat a stratum-corneum piercing microprojection, or a plurality of stratum-corneum piercing microprojections of a delivery device, for delivery of the biocompatible coating through the skin of a subject, thus providing an effective means of delivering the peptide therapeutic agents.

Described and claimed herein are methods for producing chemically stabilized Aβ protofibrillar aggregates, and compositions made therefrom. Compositions produced are useful in facilitating detailed studies of Aβ protofibril structure, fibril formation, and progression of Aβ related diseases, e.g., Alzheimers disease. In addition, chemically stabilized protofibrillar structures can be used as tools to generate and / or screen for antibodies specific for protofibrils. Antibodies specific for protofibrils can be used as diagnostic tools or as therapeutics in the diagnosis or treatment of, e.g., Alzheimer's disease. Finally, chemically stabilized protofibrillar structures can be used in the preparation of therapeutic or prophylactic vaccines.

Methods and compositions which are useful in the treatment of amyloidosis. In particular, methods and compositions are provided for inhibiting, preventing and treating amyloid depositions, e.g. in pancreatic islets, wherein the amyloidotic deposits are islet amyloid polypeptide (IAPP)-associated amyloid deposition or deposits. The methods of the invention involved administering to a subject a therapeutic compound which inhibits IAPP-associated amyloid deposits. Accordingly, the compositions and method of the invention are useful for inhibiting IAPP-associated amyloidosis in disorders in which such amyloid deposition occurs, such an diabetes. The invention also provides a process for the preparation of cells suitable for transplantation into a mammal, which cells are capable of forming fibrils, said process comprising contacting the cells with an inhibitor of fibril formation. In particular the process prepares cells for use in a method of treating diabetes. Also provided are a culture medium comprising the inhibitor and cells for transplantation.

The invention relates to the field of biochemistry, molecular biology, structural biology and medicine. More in particular, the invention relates to cross-β structures and the biological role of these cross-β structures.

The invention provides methods for designing peptides that inhibit aggregation in target polypeptides. The candidate inhibitory peptidic compounds have an oligomeric sequence that forms energetically-favorable interactions with the amino acid sequence of the steric zipper region of the target protein, and also possess a zipper-disrupting feature that disrupt the peptide stacking at the steric zipper region. This method can be used to obtain inhibitory peptides to disrupt fibril formation involving any protein for which a steric zipper sequence can be identified. The invention also provides inhibitory peptidic compounds, which can be used in pharmaceutical compositions and methods for treating polypeptide aggregation-associated diseases or conditions.

The present invention provides a therapeutic method for removing amyloid fibrils from a patient. The present invention also provides a transgenic animal that develops systemic AA amyloidosis within three weeks for use as a tool to investigate AA amyloidosis and to evaluate agents that may be potentially useful in preventing and treating amyloid-related disorders. Further, the present invention provides diagnostic assays for monitoring immunoglobulin light chain fibrillogenesis in real-time and for identification of the chemical nature of the protein in amyloid deposits which enables the determination of the type of amyloidosis for therapeutic and prognostic purposes.

An apparatus for water treatment which comprises a means of removing ingredients contained in water and a means of adsorbing ions with a porous molding as an adsorbent, wherein the porous molding comprises fibrils comprising an organic polymer resin and an inorganic ion adsorbent. The fibrils form interconnecting pores open to the outer surface and have voids in inner parts thereof, at least part of the voids being open to the surface of the fibrils. The inorganic ion adsorbent has been deposited on the outer surface of the fibrils and on the surface of the voids in the fibrils.

Polyhydroxylated aromatic compounds, and compositions containing them, are useful for the treatment of amyloidosis, especially Alzheimer's disease, and for the treatment of diseases characterized by α-synuclein fibril formation, especially Lewy body disease and Parkinson's disease.

Described is a new class of small molecule inhibitors of amyloid beta protein (Abeta) aggregation, based on apomorphine. These molecules target the nucleation phase of Abeta self-assembly and interfere effectively with aggregation of Abeta 1-40 into amyloid fibrils in vitro as determined by transmission electron microscopy, Thioflavin T (ThT) fluorescence, and velocity sedimentation. Structure-activity studies using apomorphine analogues demonstrate that 10,11-dihydroxy substitutions of the D ring are preferred for the inhibitory effectiveness of these aporphines, and that methylation of these hydroxyl groups reduces their inhibitory potency. The ability of these small molecules to inhibit Abeta amyloid fibril formation appears to be linked to their ability to undergo auto-oxidation in solution, implicating an auto-oxidation product as the active Abeta inhibitor. Sedimentation velocity and electron microscopy studies demonstrate that apomorphine and analogues facilitate oligomerization of Abeta into short nonfibrillar soluble assemblies, but inhibit Abeta fibrillization.

The invention relates to the field of biochemistry, molecular biology, structural biology and medicine. More in particular, the invention relates to cross-β structures and the biological role of these cross-β structures. In one embodiment, the invention discloses a method for modulating extracellular protein degradation and / or protein clearance comprising modulating cross-β(beta) structure formation (and / or cross-β structure-mediated activity) of the protein present in the circulation.

The invention relates to the field of biochemistry, molecular biology, structural biology and medicine. More in particular, the invention relates to cross-β structures and the biological role of these cross-β structures.

A method of preventing or treating an amyloid-β-related disease in an individual, the method comprising administering to an individual in need thereof an effective amount of a first therapeutic agent for preventing or treating an amyloid-β-related disease, and a second A therapeutic agent, the second therapeutic agent being (i) a peptide or peptidomimetic compound that modulates amyloid-beta fibril formation or induces a prophylactic or therapeutic immune response against amyloid-beta fibril formation, or (ii) Immune system modulator that prevents or inhibits amyloid-beta fibril formation.

Screening methods for identifying substances that provide therapeutic value for various diseases associated with protein misfolding are provided. Genetic and chemical screening methods are provided using a yeast system. The methods of the invention provide a rapid and cost-effective method to screen for compounds that prevent protein misfolding and / or protein fibril formation and / or protein aggregation which includes numerous neurodegenerative diseases including Parkinson's disease, Alzheimer's disease, Huntington's disease as well as non-neuronal diseases such as type 2 diabetes.

Techniques for the production of flow-oriented collagen gels using hydrodynamics to influence the assembly of collagen fibers. Highly concentrated monomeric solutions of collagen are subjected to shear and extensional flow as they are drawn onto a substrate to induce fibrillogenesis under a high Ph buffer. The produced gel captures the flow induced ordering of molecular collagen upon fibril formation. The depositing or the induction of fibrillogenosis occurs without the application of a magnetic field to the concentration of collagen. These highly oriented 3D scaffolds are capable inducing contact guidance and guiding mammalian cell growth. The collagen fibers mimic the construction of in vivo fibers with the characteristic D-periodicity and the integrin receptors on the fibroblasts respond to this organization. The industrial applications of three-dimensional collagen gels as a biomaterial are widespread from drug delivery to burn repair or tissue engineering system.

The invention provides methods for designing peptides that inhibit aggregation in target polypeptides. The candidate inhibitory peptidic compounds have an oligomeric sequence that forms energetically-favorable interactions with the amino acid sequence of the steric zipper region of the target protein, and also possess a zipper-disrupting feature that disrupt the peptide stacking at the steric zipper region. This method can be used to obtain inhibitory peptides to disrupt fibril formation involving any protein for which a steric zipper sequence can be identified. The invention also provides inhibitory peptidic compounds, which can be used in pharmaceutical compositions and methods for treating polypeptide aggregation-associated diseases or conditions.

The invention relates to a preparation method of steroid saponin, sesquiterpenoid, phenylpropanoid glycoside and phenolic acid monomeric substances in Chinese Trillium tschonoskii Maxim. and rhizoma paridis medicinal materials and application of the monomeric substances to the preparation of medicine for treating Alzheimer disease. The monomeric substances are steroid saponin, sesquiterpenoid, phenylpropanoid glycoside and phenolic acid monomeric compounds obtained by separating, purifying and refining 30-85% ethanol elution parts of macroporous adsorption resin on the total extract of the roots and tubers, fruit or whole herb of Chinese Trillium tschonoskii Maxim. and rhizoma paridis, and the monomeric substances have biological activity on inhibiting Abeta fibril formation and stopping fibril aggregation. Due to the fact that the monomeric substances have common identical or similar mother-nucleus-structure units such as Pennogenin, Trillium tschonoskii Maxim. sapogenin, diosgenin, sterol sapogenin, furostan sapogenin and sesquiterpene aglycone, the monomeric substances have similar curative effect on the Alzheimer disease.

The present invention relates to preventives or remedies for Alzheimer's disease, or to amyloid protein fibril-formation inhibitors, which include as an active ingredient a compound of general formula (I) below or a pharmacologically permitted salt thereof; and also to nitrogen-containing heteroaryl derivatives having specific substituents, or pharmacologically permitted salts thereof, which are valuable as preventives or remedies for Alzheimer's disease, or as amyloid protein fibril-formation inhibitors:(where, R1 and R2 are H or alkyl; Z1 and Z2 are H, alkyl, alkoxy, haloalkyl or halogeno; Z3 is alkoxy, SH, alkylthio, NH2, mono- or di-alkylamino, OH or halogeno; Z4 and Z5 are H or halogeno; and A is 4,6-pyrimidine-1,3-diyl, 1,3,5-triazine-2,6-diyl, etc).

The invention discloses the use of erigeron breviscapus extract for the preparation of medicaments for inhibiting beta-amyloid peptide accumulation and fibril formation. The erigeron breviscapus extract is total phenol extract prepared by extracting the whole plant of erigeron breviscapus, and contains flavonoids compounds and caffeoylquinic acid esters compounds. Experimental researches show that the erigeron breviscapus extract can remarkably inhibit the accumulation of A beta1-42, intracellularly improve apoptosis and inflammation induced by the A beta1-42 and reduce intracellular oxidative stress by clearing reactive oxygen species (ROS) such as malondialdehyde (MDA) so as to achieve the effect of protecting nerve cells and improve the activity of the nerve cells; in addition, the erigeron breviscapus extract has low toxicity to the nerve cells; and therefore, the erigeron breviscapus extract can be used for the preparation of the medicaments for treating or preventing related diseases caused by the beta-amyloid peptide accumulation and the fibril formation.

Disclosed are peptides that contain up to about 35 amino acids, including a plurality of aromatic amino acid residues and either (i) an amino acid residue that is phosphorylated or sulfated, or (ii) an amino acid comprising an ester-moiety linked via peptide bond, or both (i) and (ii), wherein the peptide is capable of self-assembly to form nanofibrils in the presence of an enzyme that hydrolyzes the phosphate group, the sulfate group, or the ester-moiety. These peptides are enzymatically responsive hydrogelators, and they can be used to form pericellular hydrogels / nanofibrils upon exposure to target cells that secrete or express a surface bound ectoenzyme having hydrolase activity suitable to induce peptide gelation. These materials, and compositions containing the same, can be used for in vitro and in vivo cellular imaging, treating cancerous conditions, collecting a secretome from a cell upon which the pericellular hydrogels / nanofibrils form, and screening the collected secretome.

The present invention resides in a method for producing jellyfish collagen hydrogels and kits for producing the same. The jellyfish collagen hydrogels can be used in the culture of cells. According to the invention, there is a process for producing jellyfish collagen hydrogels comprising jellyfish collagen fibrils, said process comprising the steps of: mixing a solution of purified jellyfish collagen and an aqueous neutralisation buffer; and incubating the mixture for a sufficient time to enable jellyfish collagen fibrils to form, wherein a cross-linking agent is either added during to mixing step or during or after the incubation of the mixture.

The invention relates to the technical field of plant tissue culture and particularly discloses an embryo-tissue-culture rapid propagation method for epimedium sagittatum. The method comprises the steps of taking an embryo of the epimedium sagittatum as an explant, carrying out procedures such as complete-dried seed disinfection, seed low-temperature culture, explant callus generation inducing, callus adventitious-bud or cluster-bud differentiation inducing, bud fibril formation inducing, seedling hardening and seedling raising so as to obtain regenerated seedlings of epimedium sagittatum, andestablishing a rapid propagation system for plant tissue culture of the epimedium sagittatum. The method has the advantages that the operation is simple, the pollution rate is low, the cycle of propagation is short, the rate of propagation is high, the cost is low, and the field survival rate of young seedlings is high, so that a technical support is provided for factory production of the epimedium sagittatum, and the method has a certain promoting action on protecting wildlife resources of the epimedium sagittatum.

The invention provides monomeric and oligomeric amyloid beta peptide isomers that are resistant towards fibrillogenesis and their use as screening reagents or antigens in methods and pharmaceutical preparations for the treatment of Alzheimer's disease and other conditions related to protein misfolding. The alanines at positions 21 and 30, in wild type amyloid beta peptide amino acid sequence, are according to the invention replaced by cysteins, which results in an intra molecular disulphide bond. The invention further provides transgenic animals expressing modified amyloid precursor proteins or amyloid beta peptides.

New antifibrillogenic agents and compositions containing same, methods of using the antifibrillogenic agents and compositions for inhibiting amyloid fibril formation, and effective therapeutics for preventing or delaying the progression of, e g., Alzheimer's disease and diabetes.

Polyhydroxylated aromatic compounds, and compositions containing them, are useful for the treatment of amyloidosis, especially Alzheimer's disease, and for the treatment of diseases characterized by α-synuclein fibril formation, especially Lewy body disease and Parkinson's disease.

The invention relates to an application of fructus gardeniae and ethanol eluting part memory-improving assisting capsules or tablets for preparing health-care foods for assisting in improving a memory function. The prepared fructus gardeniae and 30% ethanol eluting part memory-improving assisting capsules or tablets comprise the following raw material components of total monoterpenoid compounds of which the total content is greater than 90% and which is prepared through purifying 30% ethanol eluting parts of fructus gardeniae fruit total extracts through macroporous resins by a polyamide column chromatography method, wherein the total monoterpenoid compounds have the effect of assisting in improving the memory function on hypomnesis of senile physiological brain senescence caused by brain senescence, sleep disorders and A beta fibril formation and aggregation; and the prepared fructus gardeniae and 80% ethanol eluting part memory-improving assisting capsules or tablets comprise the components of 80% ethanol eluting parts of fructus gardeniae fruit total extracts, obtained through macroporous resins, wherein the 80% ethanol eluting parts have the effect of assisting in improving the memory function on hypomnesis of senile pathological brain senescence caused by brain senescence, brain hypoperfusion formed by blood vessel damage factors, and A beta fibril formation and aggregation.

Described is a new class of small molecule inhibitors of amyloid β protein (Aβ) aggregation, based on apomorphine. These molecules target the nucleation phase of Aβ self-assembly and interfere effectively with aggregation of Aβ 1-40 into amyloid fibrils in vitro as determined by transmission electron microscopy, Thioflavin T (ThT) fluorescence, and velocity sedimentation. Structure-activity studies using apomorphine analogues demonstrate that 10,11-dihydroxy substitutions of the D ring are preferred for the inhibitory effectiveness of these aporphines, and that methylation of these hydroxyl groups reduces their inhibitory potency. The ability of these small molecules to inhibit Aβ amyloid fibril formation appears to be linked to their ability to undergo auto-oxidation in solution, implicating an auto-oxidation product as the active Aβ inhibitor. Sedimentation velocity and electron microscopy studies demonstrate that apomorphine and analogues facilitate oligomerization of Aβ into short nonfibrillar soluble assemblies, but inhibit Aβ fibrillization.