Abstract: This disclosure provides a multi-target fusion protein composed of a TNF-? antagonist domain and another binding domain antagonistic for a heterologous target, such as IL6, RANKL, IL7, IL17A/F, TWEAK, CSF2, IGF1, IGF2 or BLyS/APRIL, or agonistic for a heterologous target, such as IL10. The multi-specific fusion protein may also include an intervening domain that separates the binding domains and allows for dimerization. This disclosure also provides polynucleotides encoding the multi-specific fusion proteins, compositions of the fusion proteins, and methods of using the multi-specific fusion proteins and compositions.

Abstract: The subject invention concerns materials and methods for treating a person or animal having cognitive impairment. In one embodiment, the method comprises administering an effective amount of one or more inflammatory mediator(s), for example, fms-related tyrosine kinase 3 (Flt3) ligand, interleukin-6 (IL-6), macrophage migration inhibitory factor (MIF), interleukin-1 (IL-1), interleukin-3 (IL-3), erythropoietin (EPO), vascular endothelial growth factor A (VEGF-A), hypoxia-inducible transcription factor (HIF-1alpha), insulin like growth factor-1 (IGF-1), tumor necrosis factor (TNF), granulocyte colony-stimulating factor (G-CSF), granulocyte/macrophage colony-stimulating factor (GM-CSF), macrophage colony-stimulating factor (M-CSF), Stem Cell Factor (SCF), Darbepoetin (ARANESP), and metalloproteinases, to an animal or person in need of treatment.

Abstract: The present invention provides models for studying the development of, and/or pathologies associated with neurodegenerative diseases, and agents that can modulate such development and/or pathologies.

Abstract: Disclosed herein are methods and compositions related to GHS-R antagonists.

Abstract: There are provided Idbf (inhibitor of Dvl and Bone formation) which is a novel Dvl-binding protein that binds to Dvl to inhibit signal transduction carried out through the Wnt/?-catenin signaling pathway, a gene for coding for the same, the use thereof, and the use of an inhibitor of the Idbf. The Idbf was known to be expressed by activation of the Wnt/?-catenin signaling pathway and bind to Dvl to block signal transduction carried out through the Wnt/?-catenin signaling pathway. Therefore, the Idbf can be used in development of medicines for inhibiting the signal transduction carried out through the Wnt/?-catenin signaling pathway, and an Idbf inhibitor can be used in preparation of medicines for activating the signal transduction carried out through the Wnt/?-catenin signaling pathway.

Abstract: This invention relates to a non-coding RNA (ncRNA) sequence from Human cytomegalovirus (HCMV) (termed “TRL4”) that specifically protects neuronal cells from cell death and may therefore be useful in the treatment of neurodegenerative disorders, such as Parkinson's disease.

Abstract: This invention provides methods and reagents for promoting neurogenesis, by modulating neural stem cell proliferation and differentiation. Particularly, this invention provides methods and reagents for promoting neurogenesis in a patient's central nervous system where the patient suffers from an aging-related neurodegenerative disease. Specifically, the invention provides methods for promoting neurogenesis comprising modulating the ? and/or ?-secretase activities.

Abstract: The present invention provides a method for modulating the activity of Rac1, comprising modifying the phosphorylation state of Ser179 in syndecan-4 through influencing the interaction between syndecan-4 and the guanin nucleotide exchange factor of Rac1 (RacGEF) named Tiam1 in a GTP-dependent manner. In particular, methods are provided for enhancing the epithelial phenotype of a cell and for initiating the polarization of a cell by increasing the de-phosphorylation of said Ser179 of syndecan-4, and for enhancing the migratory phenotype of a cell and for initiating the neuronal differentiation of a cell by increasing the phosphorylation of said Ser179 of syndecan-4. Polypeptides for use in modulating the activity of the small GTPase Rac are also provided, as well as a method for identifying an agent capable of indirectly modulating the activity of the small GTPase Rac 1.

Abstract: The present invention is directed to method of modulating a heat shock response in a first cell of a multicellular organism comprising stimulating or inhibiting an HSR signaling activity of a second cell, wherein the second cell is a neuronal cell that regulates heat shock response activation in the first cell and that does not directly innervate the first cell.

Abstract: The invention provides a stable metastin derivative having excellent biological activities (a cancer metastasis-inhibiting activity, a cancer proliferation-inhibiting activity, a gonadotropin secretion-promoting activity, a sex hormone secretion-promoting activity, etc.). By replacing the constituent amino acids of metastin with specific amino acids in the metastin derivative of the present invention, the blood stability and solubility of the metastin derivative can be more improved, the gel tendency of the metastin derivative can be reduced, the pharmacokinetics of the metastin derivative can be improved, and the metastin derivative can exhibit an excellent cancer metastasis-inhibiting activity and cancer proliferation-inhibiting activity. The metastin derivative can also exhibit a gonadotropin secretion-inhibiting activity, a sex hormone secretion-inhibiting activity, etc.

Abstract: The present invention relates to the field of therapeutic use of proteins, genes and cells, in particular to the therapy based on the biological function of a secreted therapeutic protein, METRNL, in particular for the treatment of disorders of the nervous system. METRNL is a Nerve Survival and Growth factor with neuroprotective and/or neurogenesis effects.

Abstract: Soluble proteins, e.g. thrombospondins, can trigger synapse formation. Such proteins are synthesized in vitro and in vivo by astrocytes, which therefore have a role in synaptogenesis. These thrombospondins are only expressed in the normal brain exactly during the period of developmental synaptogenesis, being off in embryonic brain and adult brain but on at high levels in postnatal brain. Methods are provided for protecting or treating an individual suffering from adverse effects of deficits in synaptogenesis, or from undesirably active synaptogenesis. These findings have broad implications for a variety of clinical conditions, including traumatic brain injury, epilepsy, and other conditions where synapses fail to form or form inappropriately. Synaptogenesis is enhanced by contacting neurons with agents that are specific agonists or antagonists of thrombospondins. Conversely, synaptogenesis is inhibited by contacting neurons with inhibitors or antagonists of thrombospondins.

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: This invention relates to novel protein transduction domains (PTDs) derived from secretory leukocyte protease inhibitor (SLPI). SLPI-derived PTDs are able to deliver cargo moieties in vivo and in vitro into the cytoplasm and nucleus of a host cell. The invention also relates to a transduction complex comprising one or more SLPI-derived PTDs linked or fused to one or more cargo moieties, which may comprise, for example, proteins, nucleic acids, lipids, carbohydrates, small molecules and other chemical compounds. The invention also relates to the manufacture of SLPI-derived PTDs, complexes comprising them; compositions comprising SLPI-derived PTDs or complexes; and utilization of SLPI-derived PTDs or complexes comprising them for therapeutic, diagnostic and research methods involving delivery of heterologous molecules across cellular membranes, and especially, across nuclear membranes.

Abstract: The present invention describes methods and compositions for modulating synaptogenesis and axon and/or dendritic growth. The methods include the use of agents that modulate a thrombospondin and/or an ?2? subunit of a calcium channel.

Abstract: The present invention is directed to novel soluble substrates for ?-secretase. More particularly, the invention provides a soluble fusion polypeptide with a Notch segment containing the ?-secretase-dependent cleavage sites (? and ?) fused to a NusA protein. Methods and compositions for making and using such a fusion protein are disclosed.

Abstract: The present invention discloses (1) phenolic ester hybrids of niacin with m-methoxy-p-hydroxy phenyl compounds like eugenol, vanillin, apocynin, ferulic acid, isoferulic acid and eugenol epoxide and (2) cocrystals of hybrids as above, particularly cocrystal of niacin-eugenol hybrid with cocrystal former like eugenol and oxalic acid (3) novel pharmaceutical compositions comprising a combination of niacin and one or more small molecule/potentiating agent like eugenol, curcumin, cinnamic acid, meclofenamic acid, and their use in the treatment of a disorder or a disease caused by excess production of amyloid beta peptide-42 (A?42), its deposition, accumulation, and plaque formation including Alzheimer's Disease, dementia and mild cognitive impairment as well as other neurodegenerative diseases such as Parkinson's Disease and ischemic stroke.

Abstract: The present invention relates to novel compounds comprising at most 13 contiguous amino acid residues derived from the fibronectin type 3,I1 module of neural cell adhesion molecule (NCAM), or a variant or fragment thereof, capable of interacting with an FGFR and thereby the compounds are capable of inducing differentiation, modulating proliferation, stimulate regeneration, neuronal plasticity and/or survival of cells. Further, the present invention relates to the use of said compounds for production of a medicament for treatment of conditions and diseases, wherein NCAM and/or FGFR play a prominent role.

Abstract: The present invention relates to novel 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 A

Abstract: The present invention relates to isolated Cpn10 polypeptides possessing an increased affinity for a PRR ligand compared to Ala Cpn10 polypeptide. In a further embodiment, the present invention also relates to modified chaperonin 10 polypeptides, and to nucleic acids encoding the same and to compositions comprising such polypeptides and uses thereof.

Abstract: Materials and methods for treating tissue defects in human or animal tissues using implantable cells are described. Further, culture techniques and factors for enhancing these procedures, and cell survival and adaptation are described. Many of the tissue defects may be treated with autologous cells, while applications involving non-autologous cells or stem cells are also described.

Abstract: The present invention relates to compounds of Formula I, IA, II, HA, III, or IHA and their pharmaceutical uses. Particular aspects of the invention relate to the use of those compounds for the selective inhibition of one or more caspases. Also described are methods where the compounds of Formula I, IA, II, IIA, III, or IIIA are used in the prevention and/or treatment of various diseases and conditions in subjects, including caspase-mediated diseases such as sepsis, myocardial infarction, ischemic stroke, spinal cord injury (SCI), traumatic brain injury (TBI) and neurodegenerative disease (e.g. multiple sclerosis (MS) and Alzheimer's, Parkinson's, and Huntington's diseases).

Abstract: A peptidomimetic agent from dextrorotatory amino acids includes vGek with Dval-gly-Dglu-Dlys as a central D-amino acid sequence, whereby gly is equal to D-glycine, which is equal to L-glycine. Pharmaceutical agents for use in the treatment of neurodegenerative diseases, in particular Alzheimer's disease, Parkinson's disease, Lewy Body dementia, Creutzfeldt-Jakob disease, as well as Huntington's Chorea disease, multi-system atrophy as well as disorders similar to these neurodegenerative diseases that contain at least one peptidomimetic agent from dextrorotatory amino acids are also included.

Abstract: The present invention is based on the discovery that suppressing the activity of the Nogo receptor (NgR) alone does not result in extensive axon regeneration unless the intrinsic growth program of neurons is also activated. Accordingly, the present invention is directed to methods of stimulating axon regeneration using a combination therapy wherein agents that inhibit NgR activity or downstream pathways activated by inhibitory signals are combined with agents that activate the growth pathway of neurons (e.g. polypeptide growth factors, activators of macrophages, purine nucleosides, or hexoses).

Abstract: Methods are provided for identifying agents that modulate intracellular calcium. Also provided are methods of modulating calcium within cells and methods of identifying proteins involved in modulating intracellular calcium.

Abstract: Provided herein are methods and compositions for promoting neuroprotection in a subject and for treating a neural disorder associated with protein aggregation comprising administering to the subject an agent that increases expression or activity of cathepsin-D. Also provided are methods of screening for agents that increase expression or activity of cathepsin-D and methods of screening for neuroprotective agents.

Abstract: Methods for inhibiting degeneration of a neuron, methods of treating a neurodegenerative disease, methods for promoting degeneration of a neuron are provided, methods for modulating neuron cell guidance of a neuron, as well as compounds useful in the methods of the invention, such as a Wnt compound, a Fzd3 dephosphorylating agent, a Fzd3 phosphorylating agent, or a SHH compound as disclosed herein.

Abstract: Disclosed are genes that, when overexpressed in cells expressing alpha-synuclein, either suppress or enhance alpha-synuclein mediated cellular toxicity. Compounds that modulate expression of these genes or activity of the encoded proteins can be used to inhibit alpha-synuclein mediated toxicity and used to treat or prevent synucleinopathies such as Parkinson's disease. Also disclosed are methods of identifying inhibitors of alpha-synuclein mediated toxicity.

Abstract: Disclosed are pharmaceutical compositions comprising clusterin and polypeptides substantially the same as clusterin and treatment methods for inflammatory diseases and dry eye disease. The pharmaceutical compositions include an isolated clusterin or an isolated polypeptide substantially the same as clusterin. The clusterin is preferably secreted clusterin. The method of treating dry eye disease includes administering to a patient in need an effective amount of a pharmaceutical composition comprising an isolated clusterin or an isolated polypeptide substantially the same as clusterin. The method of treating a disease state characterized by inflammation includes administering to a patient having the disease state an amount of isolated clusterin or a protein substantially the same as clusterin effective to decrease the activity of a matrix metallproteinase selected from the group consisting of MMP-9, MMP-2 and MMP-7.

Abstract: 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.

Abstract: The present invention provides stable metastin derivatives having excellent biological activities (a cancer metastasis suppressing activity, a cancer growth suppressing activity, a gonadotropic hormone secretion stimulating activity, sex hormone secretion stimulating activity, etc.). By substituting the constituent amino acids of metastin with specific amino acids, the metastin derivatives of the present invention achieve more improved blood stability, solubility, etc., reduced gelation tendency, improved pharmacokinetics, as well as exhibit an excellent cancer metastasis suppressing activity or a cancer growth suppressing activity. The metastin derivatives of the present invention also have a gonadotropic hormone secretion suppressing activity, sex hormone secretion suppressing activity, etc.

Abstract: A novel class of peptide ?-ketoamides useful for selectively inhibiting calpains, selectively inhibiting cysteine proteases, and generally inhibiting all cysteine proteases, having the formula M-AA2-AA1-CO—NH—(CH2)n—R3. Processes for the synthesis of peptidyl ?-ketoamide derivatives.

Abstract: The invention relates to a pharmaceutical or nutraceutical composition comprising an alkalized organic substance selected from the group comprising proteins, carbohydrates, lipids, amino acids, vitamins, therapeutic agents and mixtures thereof. Such compositions are useful for treating a range of diseases and conditions. They also give rise to beneficial physiological effects such as, for example, increasing physical strength, muscle mass and endurance.

Abstract: The present invention is directed to polypeptide-nucleic acid conjugates. These conjugates can allow for targeted application of a therapeutic RNAi agent across the blood-brain barrier to treat, for example, a cancer, neurodegenerative disease, or lysosomal storage disorder.

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 provides a metastin derivative represented by the formula (I): wherein each symbol is as defined in the specification, or a salt thereof, or a pharmaceutical composition containing it. The metastin derivative or a salt thereof is superior in blood stability, and has a cancer metastasis suppressive action or cancer growth suppressive action.

Abstract: The invention pertains to a liquid composition for preventing and/or treating memory decline and/or cognitive dysfunction, Alzheimer's, Parkinson's and/or dementia, said composition comprising: (i) at least 50 mg nucleoside and/or nucleotide per 100 ml; (ii) between 0.2 and 10 grams protein per 100 ml; (iii) between 0.05 and 3 wt. % of 5 thickener, based on total weight of the composition. The thickener is preferably selected from the group consisting of cellulose, xanthan gum, gellan gum, alginate, guar gum, locust bean gum, gum karaya, gum tragacanth, carrageenan, and mixtures thereof. The composition preferably has a loss factor tan ? between 0.1 and 100, as measured at any strain in the range of 1 100% at 0.1 Hz and 20° C. It is particularly found that a thickener selected from the group consisting of gellan gum, xanthan gum and cellulose greatly reduces sedimentation.

Abstract: The invention relates to methods for identifying novel PP1-interacting polypeptides and proteins, compounds which are able to inhibit the binding of PP1c to certain factors naturally interacting with it, especially proteins of the Bcl-2 family (such as Bcl-xL and Bcl-w).

Abstract: This invention provides novel compounds that are modulators of gamma secretase. The compounds have the formula: Also disclosed are methods of modulating gamma secretase activity and methods of treating Alzheimer's disease using the compounds of formula (I).

Abstract: Methods of suppressing the activation of microglial cells in the Central Nervous System (CNS), methods of ameliorating or treating the neurological effects of cerebral ischemia or cerebral inflammation, and methods of combating specific diseases that affect the CNS by administering a compound that binds to microglial receptors and prevents or reduces microglial activation are described. Also described are methods of screening compounds for the ability to suppress or reduce microglial activation.

Abstract: Antigen binding proteins that bind ?-amyloid peptide, in particular human ?-amyloid peptide; methods of treating diseases or disorders characterised by elevated ?-amyloid levels or ?-amyloid deposits, particularly Alzheimer's disease and diseases or disorders affecting the eye or optic nerve characterised by elevated ?-amyloid levels or ?-amyloid deposits, including age related macular degeneration and glaucoma type diseases and ?-amyloid dependent cataract formation, with said antigen binding proteins; pharmaceutical compositions comprising said antigen binding proteins; and methods of manufacture.

Abstract: The present invention relates to methods for preventing Alzheimer's disease (AD) with an A?42 mimotope and binds to an antibody specific for DAEFRH (SEQ ID NO: 1) which is a part of the naturally-occurring A?42 sequence.

Abstract: The present invention concerns methods and compositions for stably tethered structures of defined compositions, which may have multiple functionalities and/or binding specificities. Particular embodiments concern homodimers comprising monomers that contain a dimerization and docking domain attached to a precursor. The precursors may be virtually any molecule or structure, such as antibodies, antibody fragments, antibody analogs or mimetics, aptamers, binding peptides, fragments of binding proteins, known ligands for proteins or other molecules, enzymes, detectable labels or tags, therapeutic agents, toxins, pharmaceuticals, cytokines, interleukins, interferons, radioisotopes, proteins, peptides, peptide mimetics, polynucleotides, RNAi, oligosaccharides, natural or synthetic polymeric substances, nanoparticles, quantum dots, organic or inorganic compounds, etc. Other embodiments concern tetramers comprising a first and second homodimer, which may be identical or different.

Abstract: The patent refers to a screening method carried out on biological material isolated from human and/or animal organisms for determining the risk of human and/or animal pathologies expressing an anomalous deposition of ?-amyloid and/or amyloid-like substance in human and/or animal organs and tissues, based on the investigation of the punctiform mutation Ala>Val in position 2 of the ?-protein (corresponding to the Ala673Val mutation precursor of the ?-protein containing 770 amino acids) in homozygosis or in heterozygosis. The patent provides for the possibility of: (1) creating unicellular or multicellular transgenic organisms expressing the Ala673Val mutation; (2) synthesising or producing peptides with such mutation and/or their derivatives and/or nucleic acids containing the same mutation; (3) using such products for studying the pathogenesis of the pathologies characterised by anomalous deposition of ?-amyloid and/or amyloid substance and for the prevention, diagnosis and care of such diseases.

Abstract: A method for preventing a break out of a neurodegenerative disease in an individual and for treating an individual suffering from a neurodegenerative disease comprising the administration of an effective amount of an antimicrobial and neurotrophic peptide

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.

Abstract: A method is provided for introducing a GAG binding site into a protein comprising the steps: identifying a region in a protein which is not essential for structure maintenance introducing at least one basic amino acid into said site and/or deleting at least one bulky and/or acidic amino acid in said site, whereby said GAG binding site has a GAG binding affinity of Kd?10 ?M, preferably ?1 ?M, still preferred ?0.1 ?M, as well as modified GAG binding proteins.

Abstract: The present invention is directed to the use of the peptide compound Ala-Glu-Lys-Lys-Asp-Glu-Gly-Pro-Tyr-Arg-Met-Glu-His-Phe-Arg-Trp-Gly-Ser-Pro-Pro-Lys-Asp-OH as a therapeutic agent for the prophylaxis and/or treatment of cancer, autoimmune diseases, fibrotic diseases, inflammatory diseases, neurodegenerative diseases, infectious diseases, lung diseases, heart and vascular diseases and metabolic diseases. Moreover the present invention relates to pharmaceutical compositions preferably in form of a lyophilisate or liquid buffer solution or artificial mother milk formulation or mother milk substitute containing the peptide Ala-Glu-Lys-Lys-Asp-Glu-Gly-Pro-Tyr-Arg-Met-Glu-His-Phe-Arg-Trp-Gly-Ser-Pro-Pro-Lys-Asp-OH optionally together with at least one pharmaceutically acceptable carrier, cryoprotectant, lyoprotectant, excipient and/or diluent.

Abstract: The present invention relates to a method for treating, preventing or ameliorating a chronic neurodegenerative disorder, in particular progressive muscular atrophy (PMA), said method comprising administering to a subject in need of such a treatment, prevention or amelioration a specific inhibitor of a caspase I-dependent cytokine. Also specific inhibitors of a caspase I-dependent cytokine for treating, preventing or ameliorating a neurodegenerative disorder, in particular PMA, are disclosed herein. Furthermore, the present invention provides for the use of (a) specific inhibitor(s) of a caspase I-dependent cytokine in the medical or pharmaceutical intervention of neurodegenerative disorders.

Abstract: The invention provides a novel human protein, FISH adaptor protein, involved in amyloid ?-protein-mediated cell death. Also provided are methods for modulating amyloid ?-protein-mediated cell death using agents that interfere with the activity of FISH adaptor protein.