Abstract: The present invention relates to isolated polypeptides comprising the amino acid sequence of residues 378-413 of Mus musculus ?-1-antitrypsyn (serpina1c), and active fragments thereof, and to pharmaceutical compositions comprising same. The compositions of the invention are useful for treating burns, inflammatory, autoimmune and degenerative diseases.

Abstract: This invention relates to methods of treating Alzheimer's disease or symptoms thereof, and amnesic mild cognitive impairment or symptoms thereof. Methods of the invention include administering a therapeutically effective amount of tissue kallikrein, variants or active fragments thereof. The invention further relates to uses of tissue kallikrein or a variant or active fragment thereof for the digesting or cleaving amyloid and the treatment of conditions benefiting from the digestion or cleavage of amyloid. The invention further relates to pharmaceutical compositions comprising a therapeutically effective amount of tissue kallikrein, variants or active fragments thereof formulated for oral or intranasal administration.

Abstract: Disclosed herein are methods, and compositions for inhibiting neurodegeneration, e.g., in neuronal cells. The methods and compositions the invention can be used to treat a neurodegenerative disorder, e.g., Alzheimer's disease, Parkinson's disease, Huntington's disease, and frontotemproal dementia. In some embodiments, the methods and compositions can be used to inhibit neurodegeneration, e.g., caused by tau-mediated synaptic neurodegeneration, encephalitis, brain trauma, or any disorder suffering from weakening synapses.

Abstract: The compounds of the present invention are non-immunosupressive cyclosporine analogue molecules that are able to bind cyclophilin. Said compounds include a modified side chain of amino acid I of cyclosporin A, consisting of an oxyalkyl having substituents R?, R1 and R2, where R? is H or Acetyl; R1 is a saturated or unsaturated straight chain or branched aliphatic carbon chain; and R2 may be a hydrogen; a unsubstituted, N substituted or NN disubstituted amide; a N substituted or unsubstituted acyl protected amine; a carboxylic acid; a N substituted or unsubstituted amine; a nitrile; a ester; a ketone; a hydroxy, dihydroxy, trihydroxy or polyhydroxy alkyl; or a substituted or unsubstituted aryl.

Abstract: A peptide sequence of the form: X(Lys,Arg)XXXXX(Arg,Lys)X, wherein Lys and Arg are replaceable and X is preferably one or more of the following amino acids: hydrophobic amino acid residues (eg Pro, Leu, Met, Ile), basic amino acid residues or threonine; and wherein the sequence is capable of engaging A? and ameliorating its SOD activity and/or metal ion binding.

Abstract: Methods and compositions for treating central nervous system diseases and disorders are disclosed.

Abstract: This invention relates generally to treating synucleinopathies in subjects that are not clinically diagnosed with a lysosomal storage disease, as well as associated methods of making medicaments and screening methods.

Abstract: The present invention relates to the field of protein misfolding diseases and thus to diseases which are associated with or induced by abnormal or pathogenic three-dimensional folding of proteins and/or peptides or which are linked to pathogenic conformational changes of proteins and/or peptides, such as Alzheimer's disease. Particularly, the present invention provides novel trimeric pyrazole compounds, which exhibit a therapeutic effectiveness in regard to the aforementioned protein misfolding diseases, and refers to their use for the treatment of such protein misfolding diseases, especially neurodegenerative diseases as well as to medicaments or pharmaceutical compositions comprising these compounds.

Abstract: Methods are provided for enhancing myelination. Myelination is enhanced by administration of agents that are inhibitors of ?-secretase. Methods of screening for pharmaceutically active compounds that enhance myelination, and for genes involved in myelination are also provided.

Abstract: In one or a plurality of embodiments, there is provided a target molecule of amylospheroid, which is expressed in mature neurons and to which the amylospheroid binds to induce death of cells. Further, in one or a plurality of embodiments, there is provided a method and a substance for inhibiting death of mature neurons induced by the amylospheroid. In one aspect, the present disclosure relates to a use of Na+/K+-ATPase ?3 as a binding target molecule of amylospheroid. In another aspect, the present disclosure relates to a method for suppressing death of mature neurons induced by the amylospheroid, including inhibiting protein-protein interaction between the amylospheroid and the Na+/K+-ATPase ?3, and the like.

Abstract: An isolated protein is provided for use in treatment of a condition selected from the group consisting of Alzheimer's disease, familial Danish dementia and familial British dementia in a mammal, including man. The isolated protein is selected from the group consisting of proteins comprising an amino acid sequence having at least 70% identity to residues 90-236 of Bri2 from human; and proteins comprising an amino acid sequence having at least 70% identity to any one of the Brichos domains of Bri2 from human, chimpanzee, bovine, pig, mouse and rat.

Abstract: The present invention relates to uses of a construct consisting of virus-like particle (VLP) structure chemically coupled to a fragment of the A?-1-42 peptide and its pharmaceutically acceptable salts (hereinafter CONSTRUCT), in particular to dosage regimens, modes of and dosage forms for the administration of a CONSTRUCT for the treatment of patients suffering from dementia, in particular dementia of the Alzheimer's type.

Abstract: Agents for treating Alzheimer's disease comprising a peptide according to sequence no. 1 which binds to A? oligomers and thus results in the healing or alleviation of Alzheimer's disease. In further embodiments peptides are provided which contain a sequence no. 1, but have preceding sequence sections which allow the peptide to be secreted. For the purpose of gene therapy, corresponding DNA sequences and vectors, in particular according to sequences 3 to 6, are provided.

Abstract: An isolated oxidation-resistant ApoA1 variant dimer includes a first oxidation-resistant ApoA1 variant polypeptide monomer and a second oxidation-resistant ApoA1 variant polypeptide monomer, wherein at least one of the first and the second monomers comprises at least one amino acid substitution of a tryptophan residue for an oxidation resistant amino acid, or a functional fragment or variant thereof. Methods for treating a disease or disorder comprises administering to a subject in need thereof, a therapeutically effective amount of an isolated oxidation-resistant ApoA1 variant dimer, an oxidation-resistant ApoA1 variant monomer, an oxidation-resistant ApoA1 monomer-lipid complex, a lipid complexed oxidation-resistant ApoA1 variant monomer, a lipid complexed oxidation-resistant ApoA1 variant dimer, or combinations thereof to the subject to enhance cholesterol efflux activity in the presence of an oxidant.

Abstract: Disclosed herein is a composition for the treatment and/or prevention of Alzheimer's disease and the delivery thereof. The composition comprises a PEG hydrogel having bound thereto a capture peptide, wherein the capture peptide is capable of binding beta-amyloid. In another embodiment, the capture peptide is attached to a solid support.

Abstract: The subject technology relates, in part, to a method of treating Alzheimer's Disease (AD), early-stage AD, elevated risk of AD, mild cognitive impairment (MCI), or other forms of age-related cognitive decline in a subject in need thereof by administering to the subject a molecule that promotes calcium-release stabilization in ryanodine receptors (RyRs) and/or inosital triphosphate receptors (InsP3Rs) in brain cells. Diagnostic methods using calcium-release stabilizing immunophilins, junctophilins or calmodulin are also disclosed.

Abstract: N-(aminoacyl)-amino compound, represented by the following formula Wherein R1 denotes hydrogen, low alkyl or carbonyl, and N1 denotes an NH group and R2 denotes hydrogen or low alkylphenyl or aralkyl or imidazoalkyl or indolylalkyl, R1 and R2 together may complete a pyrrolidine or piperidine or thiazolidine ring and R3 denotes hydrogen or methyl or low alkyl and R4 denotes hydrogen or alkyl or the group remaining on exclusion of R4 from the formula and Z is a straight chain or branched alkylene, which may contain up to 3 carbon atoms. and R5 is nitrogen or sulphur or oxygen or salts thereof and ester compounds, characterised in that A is an ester or amino acid or alternatively sodium or a potassium salt of arginate and/or of ornithate and/or of aspharaginate.

Abstract: The invention relates to the use of the PAT nonapeptide in the manufacture of a drug for preventing or treating a neurodegenerative disease such as Alzheimer's disease. The parenteral route of administration is preferable, including the subcutaneous, intraperitoneal, intravenous or intranasal routes. The invention also relates to an injectable formulation containing the PAT nonapeptide which can be administered to patients suffering from a neurodegenerative disease such as Alzheimer's disease.

Abstract: The present invention is related to a structural protein of a parvovirus with an amino acid insertion at the insertion site I-453, a library comprising the protein, a multimeric structure comprising the protein, a nucleic acid encoding the protein, a vector, virus, or cell comprising the nucleic acid, a process for the preparation of the protein, a medicament comprising the protein, nucleic acid, or multimeric structure as well as methods and uses involving the protein, nucleic acid, or multimeric structure.

Abstract: Enclosed is an antagonist, which includes a peptide chain represented by an amino acid sequence. The amino acid sequence has a short sequence, C-X1X2X3X4X5-N, which is situated before and neighbored to the third cysteine (Cys, C) of the N-terminus, wherein X1 is an amino acid with aromatic ring, hydrophobic property or long chain, and X2, X3, X4 and X5 are glutamine (G), serine (S), alanine (A) and proline (P) respectively. In one embodiment, X1 is phenylalanine (F). The present antagonists can be used to inhibit or treat with the diseases caused by the activated cells expressing CXCR1 and/or CXCR2 receptor, for example, the acute or chronic inflammatory reaction induced with polymorphonuclear neutrophils (PMNs) expressing CXCR1 and/or CXCR2 receptor, and angiogenesis accompanied by tumor growth inhibition.

Abstract: Provided herein are peptoids capable of inhibiting or reversing amyloid ? (A?) fibril or plaque production. The peptoids form a helical structure with three monomers per helical turn and have at least two monomers with a side-chain having an arylalkyl group having the same chirality positioned such that the side-chains are on the same side of the peptoid. Also provided are methods of using the peptoids to inhibit or reverse aggregation of A? and methods of treating subjects with Alzheimer's disease (AD) or slowing the progression of AD.

Abstract: The present invention relates to a method for treating an individual having Alzheimer's Disease by using pharmacological chaperones that bind presenelin and thereby increase ?-secretase activity.

Abstract: The present disclosure relates to genetic markers and methods of diagnosing and screening for late-onset Alzheimer's disease (LOAD). As such, the disclosure encompasses a whole-genome association analysis of single nucleotide polymorphisms (SNPs) of which a number are located within the GRB2-associated binding protein 2 (GAB2) gene as well as other markers associated with other genes. The disclosure identifies two novel haplotypes within the GAB2 gene, i.e., a LOAD risk-enhancing and a LOAD risk-decreasing haplotype. These haplotypes modify LOAD risk differentially in combination with APOE alleles. Further encompassed are therapeutic methods and agents of decreasing the deterioration of cells associated with LOAD.

Abstract: The present invention is directed to pharmaceutical agents and compositions useful for the treatment and prevention of amyloid disease in a subject. The invention further relates to isolated antibodies that recognize a common conformational epitope of amyloidogenic proteins or peptides that are useful for the diagnosis, treatment, and prevention of amyloid disease.

Abstract: The invention relates to a purified antibody or fragment thereof that specifically binds an A? protofibril. The invention further relates to a composition that includes such antibodies. The invention also relates to using such antibodies and compositions for treating a patient having of suspected of having Alzheimer's disease.

Abstract: The present invention relates to antisense oligonucleotides that modulate the expression of and/or function of a Sirtuin (SIRT), in particular, by targeting natural antisense polynucleotides of a Sirtuin (SIRT). The invention also relates to the identification of these antisense oligonucleotides and their use in treating diseases and disorders associated with the expression of Sirtuins (SIRT)s.

Abstract: The invention relates to isolated peptides and chimeric polypeptides derived from Saposin A that have anti-angiogenic activity. These peptides are small, consisting essentially of at least 10 consecutive amino acid residues from the 31st-50th amino acid residue of Saposin A. The invention also relates to the use of these isolated peptides and chimeric polypeptides in compositions for the treatment, prevention, and inhibition of angiogenesis-related diseases and disorders such as cancer and cancer metastasis.

Abstract: The present invention relates to new therapeutic and diagnostic uses of soluble neuregulin-1 isoforms and polypeptides, particularly neurological disorders.

Abstract: The invention is based on the discovery that GM-CSF antagonists can be used for the treatment of a patient that has Alzheimer's disease or vascular dementia, or is at risk for developing Alzheimer's disease. Accordingly, the invention provides methods of administering a GM-CSF antagonist, e.g., a GM-CSF antibody and pharmaceutical compositions comprising such antagonists.

Abstract: This invention relates to novel analogs of pituitary adenylate cyclase-activating polypeptide (PACAP), which are agonists for the PACAP/vasoactive intestinal peptide (VIP) receptors: PAC1, VPAC1 and VPAC2 receptors. These PACAP analogs can be used as prophylactic/therapeutic agents for a wide range of medical disorders, including (but not limited to) cancer and autoimmune disease. These PACAP analogs can be coupled to suitable radionuclides and used in the localization, diagnosis and treatment of disseminated cancers and metastatic tumors, or coupled to small molecule therapeutics and used as vectors for targeted drug delivery. This invention also provides pharmaceutical compositions of one or more PACAP-like compounds of the invention either alone or in combination with one or more other prophylactic/therapeutic agents.

Abstract: Methods of modulating proteasome activity, increasing life span and neurogenesis are provided herein.

Abstract: The presently disclosed subject matter discloses isolated ADAM 10 modulating peptides and related compounds useful for studying the biological functions of ADAM 10 and for the treatment of diseases such as cancer, neurological disorders, asthma, and allergic responses, and disorders characterized at least in part by the presence of one or more of inflammation, excess cell proliferation, angiogenesis, and excess soluble CD23. In one aspect, the presently disclosed subject matter provides isolated mouse and human ADAM 10 prodomain comprising the sequence set forth in SEQ ID NOs 1-8, or a sequence having at least 95% homology to any of SEQ ID NOs 1-8 and having the functionality of modulating ADAM 10 activity.

Abstract: The disclosure relates generally to neurodegenerative disorders and more specifically to a group of presenilin/G-protein/c-src binding polypeptides and methods of use for modulating signaling and progression of Alzheimer's disease.

Abstract: The present disclosure provides peptides and constructs that inhibit mitochondrial fission, and compositions comprising the peptides or constructs. The present disclosure provides methods of reducing abnormal mitochondrial fission in a cell. Also provided are methods for designing and validating mitochondrial fission inhibitor constructs and peptides, including but not limited to, evaluating the effects of the constructs and peptides on Drp1 GTPase activity, binding of Drp1 to Fis1, reduction of mitochondrial damage, reduction in cell death, inhibition of mitochondrial fragmentation in a cell under pathological conditions, and reduced loss of neurites in primary dopaminergic neurons in a Parkinsonism cell culture.

Abstract: One aspect of the invention relates to inhibitors that preferentially inhibit immunoproteasome activity over constitutive proteasome activity. In certain embodiments, the invention relates to the treatment of immune related diseases, comprising administering a compound of the invention. In certain embodiments, the invention relates to the treatment of cancer, comprising administering a compound of the invention.

Abstract: Disclosed herein are methods for treating amyloid disease in humans by clearing amyloid peptides from one or more bodily fluids such as, e.g., blood, of a patient. In particular, the methods are based on the administration of compounds capable of binding to amyloid-beta (A?) or on dialysis of blood or plasma exchange in order to remove A? peptides from the blood circulation, and/or brain or other affected organs.

Abstract: The application reports that perlecan domain V (DV) or the LG3 domain thereof reduces deposition and toxicity of A? peptide, the major component of plaques in Alzheimer's disease. Methods of using DV, LG3 and related molecules in treatment of amyloidogenic diseases, particularly Alzheimer's disease, are provided.

Abstract: Disclosed are compounds having enhanced potency in the modulation of NMDA receptor activity. Such compounds are contemplated for use in the treatment of diseases and disorders, such as learning, cognitive activities, and analgesia, particularly in alleviating and/or reducing neuropathic pain. Orally available formulations and other pharmaceutically acceptable delivery forms of the compounds, including intravenous formulations, are also disclosed.

Abstract: Provided are ?-sheet breaker peptides binding to ? amyloid peptide (A?1-42), which have the homologous sequence with A? 14-23. ?-sheet breaker peptides can be used for the manufacture of a medicament for prophylactic and/or therapeutic treatment of Alzheimer's Disease.

Abstract: The present invention relates to amyloidogenic peptides, polypeptides and proteins; and methods for screening to identify modulators of polypeptide self-aggregation into amyloids. The invention further relates to assays and methods using islet amyloid polypeptide (IAPP) as a component of a model system with which to screen for modulators of islet amyloid formation and accumulation. Also encompassed are modulators identified using the assays and methods described herein and compositions comprising same. The present invention also relates to methods and compositions for modulating amyloid formation and accumulation, thereby providing novel treatments for amyloidoses. In a particular aspect, methods and compositions are presented for inhibiting islet amyloid formation and accumulation, thereby providing novel treatments for diabetes.

Abstract: The present invention provides novel pharmaceutical compositions comprising ApoE-derived peptide dimers. In particular, the ApoE peptide dimers of the invention comprise at least two ApoE mimetic domains and can comprise one or more protein transduction domains. Methods of treating various conditions, such as cancer, inflammatory conditions, and neurodegenerative diseases, by administering the pharmaceutical compositions of the invention are also disclosed.

Abstract: The present invention relates to novel cyclic or constrained acyclic compounds which modulate the activity of G protein-coupled receptors and are useful in the treatment of conditions mediated by G protein-coupled receptors, for example, inflammatory conditions.

Abstract: The invention relates to therapeutic agents for use in the prevention or treatment of Alzheimer's disease. In particular the invention relates to use of inhibitors of cell cycle re-entry and progression to the G1/S transition or inhibitors of progression of the cell cycle through the G1/S transition point in the prevention or treatment of Alzheimer's disease.

Abstract: The invention relates generally to chaperonin 10 N-terminal variants. More specifically, the invention relates to chaperonin 10 N-terminal variants with enhanced immunomodulatory capacity and/or enhanced binding affinity for pathogen-associated molecular patterns (PAMPs) and/or damage-associated molecular patterns (DAMPs).

Abstract: An antibody capable of recognizing amyloid ? while not recognizing amyloid ? precursor proteins, and a method for using the same. A monoclonal antibody characterized by being capable of recognizing the N-terminus peptide of amyloid ? while not recognizing amyloid ? precursor proteins, an amyloid ? assay kit, a therapeutic agent of Alzheimer's disease, and a method for treating Alzheimer's disease using the monoclonal antibody.

Abstract: Inhibition of eIF-2? phosphorylation can be used to improve cognitive function and/or to treat dementia, including Alzheimer's Disease. In particular, this can be achieved by inhibiting the kinase activity of PKR in a non-toxic manner.

Abstract: A method is provided for treatment of a condition mediated by Nox2 in a patient. The method comprises administering to the patient by inhalation a polypeptide as described herein, able to inhibit superoxide production by Nox2.

Abstract: The invention provides methods and compositions for reducing or inhibiting net beta-amyloid peptide production and/or amyloid plaque formation. The methods and compositions involve administering a netrin-1 polypeptide or netrin-1 therapeutic to a subject in need thereof.

Abstract: The present disclosure relates to peptides having a core sequence as described herein as well as application of the disclosed technology as inhibitors of caspase-2 and/or -6 activity.

Abstract: The invention relates to novel cyclic compounds which have the ability to modulate the activity of G protein-coupled receptors. The compounds preferably act as antagonists. In preferred embodiments, the invention provides cyclic peptidic and peptidomimetic antagonists of C5a receptors, which are active against C5a receptors on polymorphonuclear leukocytes and macrophages. The compounds of the invention are both potent and selective, and are useful in the treatment of a variety of inflammatory conditions.