Abstract: The method of the invention relates to a modified OmCI polypeptide or a polynucleotide encoding a modified OmCI polypeptide which lacks LK/E binding activity and the use of such polypeptides and polynucleotides for the treatment of a disease or condition mediated by complement.

Abstract: Disclosed herein are methods of diagnosing, preventing and treating Alzheimer's disease based on the use of an inhibitor for the binding of amyloid-? (A?) to Fc?RIIb, and a method of screening the inhibitor. The inhibitor is selected from the group consisting of an Fc?RIIb protein or a variant thereof, an Fc?RIIb extracellular domain, an anti-Fc?RIIb antibody, an Fc?RIIb-specific peptide and an Fc?RIIb-specific siRNA. The inhibitor reduces the toxic signaling and intracellular translocation of A? and the neurotoxicity, neuronal cell death and memory impairment mediated by A? by inhibiting the binding between A? and Fc?RIIb. Thus, the inhibitor is useful in the diagnosis, prevention and treatment of Alzheimer's disease.

Abstract: Disclosed herein are isolated peptides, pharmaceutical compositions and methods for use of such for treating subjects with a neurodegenerative disease, such as Alzheimer's. In an example, an isolated polypeptide includes a cyclin dependent kinase 5 (Cdk5) inhibitory domain that has at least 95% sequence identity to the amino acid sequence set forth as SEQ ID NO: 1, wherein the Cdk5 inhibitory domain is linked to a protein transduction domain. Methods of reducing or inhibiting one or more symptoms associated with a neurodegenerative disease by administering a therapeutically effective amount of a pharmaceutical composition including one or more disclosed peptides are also provided.

Abstract: Polypeptides and other compounds that can bind specifically to the CH2-CH3 cleft of an immunoglobulin molecule, and methods for using such polypeptides and compounds to inhibit Fc-mediated immune complex formation, Immune complexed IgG to IgG F?R binding, and immune complexed IgG mC1q (membrane C1q) or soluble C1q binding. Such compounds may have therapeutic use in treating amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD), and Alzheimer's disease (AD).

Abstract: The present disclosure provides a new technology platform that converts one type of cells (substrate cells) to another type of cells (product cells).

Abstract: Peptide-based compounds including heteroatom-containing, three-membered rings efficiently and selectively inhibit specific activities of N-terminal nucleophile (Ntn) hydrolases. The activities of those Ntn having multiple activities can be differentially inhibited by the compounds described. For example, the chymotrypsin-like activity of the 20S proteasome may be selectively inhibited with the inventive compounds. The peptide-based compounds include an epoxide or aziridine, and functionalization at the N-terminus. Among other therapeutic utilities, the peptide-based compounds are expected to display anti-inflammatory properties and inhibition of cell proliferation.

Abstract: The invention demonstrates that, contrary to apoptotic rabies virus G proteins, certain non-apoptotic rabies virus G proteins, such as the G protein of the CVS-NIV strain, have a neurite outgrowth promoting effect. The invention further demonstrates that this neurite outgrowth promoting effect is due to the cytoplasmic tail of said non-apoptotic rabies virus G proteins, more particularly to their PDZ-BS, which shows a single-point mutation compared to the one of apoptotic rabies virus G proteins. The invention provides means for inducing and/or stimulating neurite outgrowth, which are useful in inducing neuron differentiation, for example for the treatment of a neoplasm of the nervous system, as well as in regenerating impaired neurons, for example for the treatment of a neurodegenerative disease, disorder or condition or in the treatment of a microbial infection, or in protecting neurons from neurotoxic agents or oxidative stress.

Abstract: Peptide-based compounds including heteroatom-containing, three-membered rings efficiently and selectively inhibit specific activities of N-terminal nucleophile (Ntn) hydrolases. The activities of those Ntn having multiple activities can be differentially inhibited by the compounds described. For example, the chymotrypsin-like activity of the 20S proteasome may be selectively inhibited with the inventive compounds. The peptide-based compounds include an epoxide or aziridine, and functionalization at the N-terminus. Among other therapeutic utilities, the peptide-based compounds are expected to display anti-inflammatory properties and inhibition of cell proliferation.

Abstract: The present invention provides anti-inflammatory compounds, pharmaceutical compositions thereof, and methods of use thereof for treating inflammatory disorders. The present invention also provides methods of identifying anti-inflammatory compounds and methods of inhibiting NF-?B-dependent target gene expression in a cell.

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

Abstract: Methods for screening for compounds that inhibit neurodegeneration are presented. Shedding of APP can be a useful marker for neurodegeneration and compounds that inhibit shedding of APP are useful as inhibitors of neurodegeneration. Such compounds may be useful in treatment and/or prevention of various neurological diseases, disorders and neuronal damage and may enhance growth, regeneration or survival of mammalian neuronal cells or tissue.

Abstract: The present invention provides a polypeptide having a biological activity of the Chemotaxis Inhibitory Protein of Staphylococcus aureus (‘CHIPS’), the polypeptide comprising or consisting of the amino acid sequence of SEQ ID NO: 2, or a fragment or variant thereof having a biological activity of CHIPS, wherein the fragment or variant retains amino acid substitutions K40E, D42V, N77H, K100R, K105R, N111 K and/or G112A relative to the wildtype CHIPS protein of SEQ ID NO:1. In one embodiment, polypeptide consists of the amino acid sequence of SEQ ID NO: 2. Related aspects of the invention provide pharmaceutical compositions comprising a polypeptide of the invention, together with methods or making and using the same.

Abstract: Disclosed herein is a method of promoting neuronal outgrowth in a neuron. The method comprises contacting the neuron with an effective amount of hypoxanthine, to thereby promote neuronal outgrowth of the neuron. The hypoxanthine may be contacted in the absence of xanthine oxidase and/or in the absence of exogenous nerve growth factor (NGF), and/or in the absence of exogenous D-mannose, and/or in the absence of exogenous oncomodulin, and/or in the absence of exogenous TGF-B. The neuron may be an optic nerve neuron or a retinal neuron and/or an injured neuron. Neurons may be from the central nervous system (CNS) or the peripheral nervous system (PNS). The methods are useful for treating an injured neuron, for example to an optic nerve neuron, resulting from branch and central vein/artery occlusion, trauma, edema, angle-closure glaucoma, open-angle glaucoma. Methods of treatment of various neurological injuries and diseases, as well as therapeutic compositions, are also disclosed.

Abstract: This invention relates to methods of treating diseases involving accumulation of A? plaques, including Alzheimer's Disease by the peripheral administration of soluble Nogo receptor polypeptides. The invention also provides methods of increasing the plasma to brain ratio of A? peptide and enhancing A? peptide clearance via peripheral administration of soluble Nogo receptor polypeptides. This invention also provides methods of improving memory function or inhibiting memory loss via the peripheral administration of soluble Nogo receptor polypeptides. The invention also provides methods of decreasing the size and number of A? plaques in a mammal via peripheral administration of soluble Nogo receptor polypeptides.

Abstract: The invention concerns the use of a nutritional composition for the treatment of disorders which are associated with malfunctioning in the uptake and use of food-derived energy in the human body. In particular, the invention concerns the use of a nutritional composition for the treatment of a disorder, which is mediated by a postprandial endocrine or neurological response in a human body, wherein the nutritional composition comprises one or more of a specific protein fraction, a specific carbohydrate fraction and a specific nutritional fiber fraction.

Abstract: Novel iron chelators exhibiting neuroprotective and good transport properties are useful in iron chelation therapy for treatment of a disease, disorder or condition associated with iron overload and oxidative stress, e.g., a neurodegenerative or cerebrovascular disease or disorder, a neoplastic disease, hemochromatosis, thalassemia, a cardiovascular disease, diabetes, an inflammatory disorder, anthracycline cardiotoxicity, a viral infection, a protozoal infection, a yeast infection, retarding aging, and prevention and/or treatment of skin aging and skin protection against sunlight and/or UV light. The iron chelator function is provided by a 8-hydroxyquinoline, a hydroxypyridinone or a hydroxamate moiety. The neuroprotective function is imparted to the compound, e.g., by a neuroprotective peptide. A combined antiapoptotic and neuroprotective function is provided by a propargyl group.

Abstract: The invention relates to compounds of Formula I: and pharmaceutically acceptable salts and prodrugs thereof, wherein R1, R2, and R3 are defined as set forth in the specification. The compounds are agonists of neurotrophin (such as nerve growth factor) receptors.

Abstract: The present invention relates to: TNF-? antagonists containing IGFBP5 protein, variants thereof, or fragments thereof; and the use of the TNF-? antagonists. More specifically, the present invention relates to: a polynucleotide encoding the protein, variants thereof, or fragments thereof; a vector containing the polynucleotide; a transformant containing the vector; and a method for screening a therapeutic agent for TNF-? overexpression-related diseases by checking whether the mutual reaction thereof is facilitated after treating with candidates to the cell expressing the IGFBP5 protein, variants thereof, or fragments thereof, and the TNER1.

Abstract: The invention provides methods and compositions for localized delivery of a vector comprising a therapeutic agent to a specific region of the brain associated with a neurodegenerative diseases that is characterized by an excess buildup of buildup of intracellular protein aggregates. In particular, the invention provides methods and compositions used to deliver an adeno-associated virus vector (AAV) comprising a nucleotide sequence encoding an inhibitor of apoptosis protein (IAP) to cells in the region.

Abstract: The invention relates to methods and products for preventing and treating neuronal cell death-associated diseases and/or conditions. The products and methods are useful for research and for clinical applications relating to neuronal cell-death associated diseases and/or conditions.

Abstract: An object of the present invention is to provide a safe and effective method for enhancing an immune response and a medicament for preventing or treating Alzheimer disease comprising amyloid ? peptide that induces an enhanced immune response. An amyloid ? peptide or a portion thereof with addition or insertion of cysteine and a method for enhancing an immune response using the peptide or a method for enhancing an immune response using the peptide together with an adjuvant. A medicament for preventing or treating Alzheimer disease comprising an amyloid ? peptide or a portion thereof that induces an enhanced immune response. A DNA vaccine, that may have the same effect, comprising the gene encoding an amyloid ? peptide or a portion thereof that induces an enhanced immune response with addition or insertion of cysteine.

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 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: Thymosin ?4 can be used to treat neuronal and brain injuries that are accompanied by neuronal cell death or injury, including injuries caused by stroke or trauma and injuries caused by neurological and neurodegenerative disease. In particular, stroke and multiple sclerosis are examples of conditions which may be ameliorated by treatment with thymosin ?4. Thymosin ?4 has been found to restore neurological tissue through several effects on several neurological parameters which are improved by administration of thymosin ?4 to a subject in need of neurological tissue restoration. For example, thymosin ?4 improves axonal myelination, migration of neural progenitor cells, neural progenitor cell proliferation, differentiation of neural progenitor cells into mature neurons, differentiation of neural progenitor cells into mature glia, nerve regeneration, and brain remodeling at locations of brain injury.

Abstract: The invention relates to a heat shock protein from alfalfa and/or a hydrolysate of a heat shock protein from alfalfa in the manufacture of a food product for the prophylactic or therapeutic treatment of a chronic inflammatory disorder. Further, the invention relates to a clinical food product comprising heat shock protein from alfalfa and/or a hydrolysate of a heat shock protein from alfalfa.

Abstract: The present invention provides a peptide which functions as a mimic peptide of an amyloid ? peptide and is capable of inhibiting the fibrillogenesis of an amyloid ? peptide. The present invention relates to: an 8- to 30-amino acid residue peptide comprising an amino acid sequence represented by the following formula (I): X1-Asp-X2-X3-X4-Pro-X5-X6 (SEQ ID NO: 28)??(I) wherein X1 represents a branched chain amino acid, and X2, X3, X4, X5, and X6 are the same or different and each represents an ?-amino acid; a 9- to 30-amino acid residue peptide comprising an amino acid sequence represented by the following formula (III): Z1-X13-Gly-X14-X15-Pro-Trp-Met-Z2 (SEQ ID NO: 31)??(III) wherein X13, X14, and X15 are the same or different and each represents an ?-amino acid, Z1 and Z2 are the same or different and each represents cysteine or serine, and when Z1 and Z2 represent cysteine, they may be crosslinked; and a pharmaceutical composition and an amyloid ? fibrillogenesis inhibitor comprising the peptide.

Abstract: The present invention provides a method of identifying an effective agent that alters the association of a Bit1 polypeptide with an AES polypeptide. The method is practiced by contacting a Bit1 polypeptide, or active fragment thereof, and an AES polypeptide, or active fragment thereof, with an agent under conditions that allow the Bit1 polypeptide or active fragment thereof to associate with the AES polypeptide or active fragment thereof; and detecting an altered association of the Bit1 polypeptide or active fragment thereof and the AES polypeptide or active fragment thereof, where an altered association indicates that the agent is an effective agent that alters the association of a Bit1 polypeptide with an AES polypeptide. Such an effective agent can modulate apoptosis and can be a useful therapeutic agent.

Abstract: The present invention provides a metastin derivative in which the amino acids comprising metastin were modified by alternative chemical substituents resulting in metastin derivitives, having excellent blood stability and exhibiting cancer metastasis inhibiting action or cancer growth inhibiting action.

Abstract: Embodiments herein generally relate to methods, compositions and uses of CaMKII inhibitors. Other embodiments relate to methods, compositions and uses of agents that target CaMKII. Yet further embodiments relate to compositions, methods and uses of CaMKIIN-derived molecules and other CaMKII inhibitor molecules that inhibit autonomous CaMKII activity. In accordance with these embodiments, compositions that inhibit autonomous CaMKII activity may be used for treating conditions causing neuronal cell death, for treating cancer or for treating neurodegenerative disorders.

Abstract: Methods, kits, screens, assays, treatments and treatment regimes for treating a patient at risk for or suffering from dementia, and particularly Alzheimer's dementia which are based upon identification of enhanced risk by genotyping APOE and APOJ. In particular, described herein are methods for the prophylactic treatment of dementia based upon results of said genotyping. The systems and methods herein described may be used both to detect and to target the primary genetically mediated pathways associated with amyloid burden. For example, a system for deciding treatment based on previously identified genetic polymorphisms (e.g., APOE4, polymorphism in APOJ) that affect amyloid clearance is described herein; such patients may respond to treatments that modulate glial based GLT-1 (e.g., Tianeptine) and/or enhance HSP expression/activity (e.g., GGA).

Abstract: This invention relates to treatment of neurodegeneration, multiple sclerosis, or schizophrenia using an ADNF III polypeptide in combination with another therapeutic agent. Neurodegeneration, including neurodegeneration caused by dementia-related conditions, such as tauopathies, including Alzheimer's disease, and aging-related dementia, is treated by a combination of an ADNF III polypeptide and an acetylcholinesterase inhibitor. Multiple sclerosis is treated by a combination of an ADNF III polypeptide and glatiramer acetate. Schizophrenia is treated with a combination of an ADNF III peptide and an antipsychotic drug, selected from Aripiprazole, Clozapine, Ziprasidone, Resperidone, Quetiapine, and Olanzapine.

Abstract: The described invention provides methods for treating or preventing progression of a progressive cognitive disease, disorder or condition, and methods for improving resilience of cognitive function in a subject in need thereof.

Abstract: Isolated peptides are provided, being less than 20 amino acids in length. The peptides comprising an amino acid sequence GVLYVGSKTREGV (SEQ ID NO: 12) AAATGLVKREE (SEQ ID NO: 13) or GVVAAAEKTKQG (SEQ ID NO: 14), mimetics and/or fragment thereof, the peptides being capable of inhibiting alpha synuclein aggregation. Pharmaceutical compositions comprising same are also provided as well as uses thereof.

Abstract: The invention provides methods for treating inflammatory diseases by administering to the subject an effective amount of an agent that provides alpha B-crystallin activity, where the dose is effective to suppress or prevent initiation, progression, or relapses of disease, including the progression of established disease. In some embodiments, the methods of the invention comprise administering to a subject having a pre-existing inflammatory disease condition, an effective amount of alpha B-crystallin protein, to suppress or prevent relapses of the disease.

Abstract: The present invention relates to methods of treating and preventing Alzheimer's Disease or other tauopathies in a subject by administering a tau protein, its immunogenic epitopes, or antibodies recognizing the tau protein or its immunogenic epitopes under conditions effective to treat or prevent Alzheimer's Disease of other tauopathies. Also disclosed are methods of promoting clearance of aggregates from the brain of the subject and of slowing progression of tangle-related behavioral phenotype in a subject.

Abstract: The present invention relates to antisense oligonucleotides that modulate the expression of and/or function of Sirtuin 1 (SIRT1), in particular, by targeting natural antisense polynucleotides of Sirtuin 1 (SIRT1). The invention also relates to the identification of these antisense oligonucleotides and their use in treating diseases and disorders associated with the expression of SIRT 1.

Abstract: The invention is directed to a pharmacologically active peptide conjugate having a reduced tendency towards enzymatic cleavage comprising a pharmacologically active peptide sequence (X) and a stabilising peptide sequence (Z) of 4-20 amino acid residues covalently bound to X.

Abstract: Neurturin polypeptides which possess reduced heparin and heparan sulfate binding affinity but retain neurotrophic activity, nucleic acids which encode the neurturin variants and vectors and host cells which express the enhanced neurturin polypeptides. Use of the enhanced neurturin polypeptides, nucleic acids and host cells in the treatment or prevention of disease.

Abstract: The invention relates to compounds having either agonist or antagonist activities for the neurotrophins NGF and BDNF and represented by monomeric or dimeric substituted dipeptides that are analogs of the exposed portions of loop 1 or loop 4 regions of these neurotrophins near or at a beta-turn of the respective loop. N-acylated substituents of these dipeptides are biostereoisomers of the amino acid residues preceding these dipeptide sequences in the neurotrophin primary structure. The dimeric structure is produced advantageously by using hexamethylenediamine to which dipeptides are attached via their carboxyl groups. The claimed compounds displayed neuroprotective and differentiation-inducing activities in cellular models and enhanced the amount of phosphorylated tyrosine kinase A and the heat shock proteins Hsp32 and Hsp70 in the concentration range of 10?9 to 10?5 M.

Abstract: The invention refers to multibasic, N-terminally modified tetrapeptide mimetics with a C-terminal P1-arginine mimetic, methods for their production and use for therapy and prophylaxis of diseases, caused by bacterial pathogens or viruses, as well as for therapy and prophylaxis of diabetes, arteriosclerosis, cancer, Alzheimer's or the onset of obesity, as well as the use of these compounds as inhibitors of the proprotein convertases which cleave behind basic P1 residues, especially for inhibition of the protease furin.

Abstract: The present invention relates to a method of making asymmetrical bis(thiosemicarbazones), compounds useful as synthetic intermediates in the method, new bis(thiosemicarbazones) that can be readily accessed by use of the method and methods of treatment and imaging utilising some of the new bis(thiosemicarbazones).

Abstract: Prosaposin, saposin C and various peptide fragments of saposin C stimulate neurite outgrowth in vitro. In addition, prosaposin and saposin C promote increased myelination ex vivo. Prosaposin is present in large neurons of the brain, including both upper and lower motor neurons.

Abstract: The invention discloses a family of neuronal migration-inducing, proliferation-promoting and neurite outgrowth promoting factors, termed NRP compounds, and provides compositions and methods for the use of NRP compounds in the treatment of brain injury and neurodegenerative disease. NRP-1 compounds induce neurons and neuroblasts to proliferate and migrate into areas of damage caused by acute brain injury or chronic neurodegenerative disease, such as stroke, trauma, nervous system infections, demyelinating diseases, dementias, and metabolic disorders. NRP compounds may be administered directly to a subject or to a subject's cells by a variety of means including orally, intraperitoneally, intravascularly, and directly into the nervous system of a patient.

Abstract: A protein kinase C inhibitor that binds B-amyloid and its peptide derivatives with the same function are disclosed. These may be useful in the treatment of Alzheimer's disease, for example as pseudo vaccines comprising antibodies, or as part of fusion proteins which are able to pass through cell membranes or through the blood-brain barrier. Methods of using the PKC inhibitor and its peptide derivatives for treating Alzheimer's disease are also disclosed.

Abstract: The present invention relates to derivatives of L-Tyrosyl-L-Arginine and the use of said derivatives in the prevention and/or treatment of a tau-induced cytotoxicity.

Abstract: The present invention relates to compositions and methods for use in the treatment of conditions such as septicaemia and septic shock. The invention further provides compositions and methods for the suppression of Toll-like Receptor 14 interaction with CD14 during Toll-like Receptor mediated signalling. The invention further provides screening assays to identify compounds which have utility in preventing the association of Toll-like Receptor 14 and CD14.

Abstract: The present invention relates to the use of MRI monitoring of ventricular enlargement rate as an objective measure for the purpose of assessing disease progression in patients suffering from Alzheimer's disease and for the purpose of determining therapeutic effectiveness of a treatment regimen for Alzheimer's patients. Methods for treating Alzheimer's Disease and monitoring therapeutic effectiveness are provided.

Abstract: In one aspect, the invention relates to a method for identifying a drug candidate with activity as a neuroprotective agent. The method includes determining whether a compound reduces ATF4 activity; and identifying the compound that reduces ATF4 activity as a drug candidate.

Abstract: The present invention features a compound having the formula A-X-B, where A is peptide vector capable of enhancing transport of the compound across the blood-brain barrier or into particular cell types, X is a linker, and B is a peptide therapeutic. The compounds of the invention can be used to treat any disease for which the peptide therapeutic is useful.

Abstract: The present invention relates to peptides, peptidomimetic compounds and pharmaceutical uses thereof for the treatment of neurodegenerative diseases or tumourigenesis and more specifically diseases deriving from the dysregulation of the signalling system of Ambra-1-mediated autophagy.