Abstract: A method for treating a condition in a patient, wherein the condition is selected from the group consisting of Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, stroke and peripheral neuropathy. The method consists of administering to the patient a pharmaceutically effective amount of a pharmaceutical composition comprising the MANF2 polypeptide of SEQ ID NO:2 or a functional fragment thereof.

Abstract: A vaccine for delaying an onset of or for treatment of an ?-synuclein-related disorder in an individual comprises a therapeutically effective amount of isolated stabilized soluble ?-synuclein oligomer having a lower formation rate to a non-soluble aggregated form than a non-stabilized oligomer of the ?-synuclein. An antibody for delaying an onset of or for treatment of an ?-synuclein-related disorder in an individual binds soluble ?-synuclein. Methods for delaying an onset of for treatment or for prevention of an ?-synuclein-related disorder employ the vaccine or antibody. Methods of detecting ?-synuclein oligomers employ the antibody.

Abstract: The invention relates to novel neurogenin proteins, nucleic acids and antibodies.

Abstract: The present invention pertains to a method for in vitro prognosticating and/or diagnosing cerebral cerebral malaria, wherein said method comprises a step of detecting non-erythroid spectrin or fragments thereof, and/or antibodies directed against non-erythroid spectrin, in a biological sample. Reagents and kits for performing this method are also disclosed.

Abstract: The present inventors identified a selective marker 65B13 for GABA neuron progenitor cells of the spinal dorsal horn and cerebellum, and successfully isolated GABA neuron progenitor cells using antibodies that bind to a protein encoded by the gene. 65B13 was demonstrated to be useful as a marker to isolate GABA-producing neuron progenitor cells in the spinal dorsal horn and cerebellum. GABA neuron progenitor cells can be efficiently identified or isolated by using the identified marker as an indicator.

Abstract: A novel cytosolic 58 kd phosphoprotein induced during bone marrow stem cell (BM) differentiation into dendritic cells (DC) during in vitro cultivation with the cytokine GM-CSF by addition of antisera to an 82 kd BM cell surface protein generating cultivatable dendritic progenitor cells (DP). Genes, methods for preparing them as well as early DP have been provided. Potential uses/advantages lie in the study of BM differentiation and innate immunity due to stimulatory/inhibitory DC, contribution of BM and DP to inflammation during infection and carcinogenesis, tumor promotion/regression, identification of BM-derived blood cells, T-cell activation/regulation/tolerance and inflammation.

Abstract: The present invention is directed to a novel polypeptide, designated in the present application as “UCP4” (SEQ ID NO: 1), having homology to certain human uncoupling proteins (“UCPs”) and to nucleic acid molecules encoding those polypeptides. Also provided herein are vectors and host cells comprising those nucleic acid sequences, chimeric polypeptide molecules comprising the polypeptides of the present invention fused to heterologous polypeptide sequences, antibodies which bind to the polypeptides of the present invention, and methods for producing the polypeptides of the present invention.

Abstract: The invention relates to methods of treating neurological disorders in a subject, by activating a DISC1 pathway. Methods of promoting neurogenesis in adult neural progenitor cells, enhancing nerve generation and treating GSK3 disorders as well as related compositions are also provided.

Abstract: Disclosed are a method and a corresponding pharmaceutical composition for treating damaged cartilage and subchondral bone. Neurogenic compounds in general and neuropeptides in particular have been found to be highly effective in stimulated repair of cartilage and bone damaged due to traumatic injury, ligament disease, and disuse. Preferred active ingredients for use in the method and corresponding pharmaceutical composition include calcitonin gene-related peptide (CGRP), cholecystokinin (CCK), dynorphin, enkephalin, galanin, neuropeptide Y (NPY), neurotensin, somatostatin, substance P (SP), thyrotropin-releasing hormone (TRH), vasoactive intestinal peptide (VIP).

Abstract: The present invention relates to a method for diagnosing Alzheimer's disease and Parkinson's disease in a subject by analyzing the expression of Semaphorin 3 and downstream effectors. It also provides a method for identifying a substance useful in the prevention or treatment of Alzheimer's disease and Parkinson's disease, and a method of using such substance in the treatment of Alzheimer's disease and Parkinson's disease.

Abstract: This invention relates to drug screening using mammalian repulsive guidance molecules and mammalian Neogenin. In addition, the invention provides for methods of preventing, alleviating or treating various disorders of the nervous system, angiogenic disorders or disorders of the cardio-vascular system and malignancies of different etiology by disrupting the interaction between RGM and Neogenin.

Abstract: Disclosed are modified naturally occurring biocompatible biopolymers of plant and animal origin made by subjecting same to ionizing radiation in the presence of a mediating gas, typically acetylene to enable one to selectively enhance and modify one or more of the physiochemical properties of the starting materials which have a wide range of uses in medicine, food technology and other industrial applications. Notwithstanding the modifications, the biocompatibility of the biopolymer remains unchanged and no new or additional functional groups are introduced into the starting biopolymer.

Abstract: The invention relates to novel neurogenin proteins, nucleic acids and antibodies.

Abstract: The present invention provides a complex of human growth hormone and zinc containing human growth hormone and zinc at a molar ratio of about 1:1.6 to about 1:2.4, and a sustained-release preparation which comprises the complex of human growth hormone and zinc and a biodegradable polymer and which has a high entrapment ratio of human growth hormone and exhibits a stable sustained-release suppressing the initial burst.

Abstract: A novel growth factor, artemin, which belongs to the GDNF/neurturin/persephin family of growth factors, is disclosed. The human and mouse amino sequences have been identified. Human and mouse artemin genomic DNA sequences have been cloned and sequenced and the respective cDNA sequences identified. In addition, methods for treating degenerative conditions using artemin, methods for detecting artemin gene alterations and methods for detecting and monitoring patient levels of artemin are provided.

Abstract: Disclosed is a method for promoting retinal neuronal survival in a mammal, wherein the neuronal cells are at risk of dying. The method comprises administering to the mammal an effective dose of at least one of the following substances: IGF-I; a functional derivative of IGF-I; IGF-II; or a functional derivative of IGF-II.

Abstract: The present invention relates to the finding that antibodies bind to the &bgr;-amyloid peptide, and that &bgr;-amyloid peptide binds the hinge region of the immunoglobulin heavy chain, thereby preserving the ability of the immunoglobulin to bind antigen. Methods for binding compounds such as detectable groups to &bgr;-amyloid peptide are accordingly presented.

Abstract: Stable, aqueous pharmaceutical formulations of human nerve growth factor (NGF) in aqueous isotonic solutions, buffered to maintain the pH from about 4.5 to about 6.0, and optionally containing a carrier such as human serum albumin are provided. Also provided are aqueous NGF formulations suitable for lyophilization and subsequent reconstitution in which rhNGF is admixed with sugars, optionally HSA, and buffer. The formulations are useful for the treatment of Alzheimer's disease and other neuronal disorders.

Abstract: NGF variants which have trkC-binding activity and trkC-signal inducing activity are provided. The variants optionally have trkA or trkB binding and signal induction activity. The NGF variants of the present invention are useful in the treatment of neuronal disorders. Nucleic acids and expression vectors encoding the NGF variant neurotrophins are also provided.

Abstract: The present invention has found that the Mts1 protein is expressed in white matter astrocytes in the spinal cord. Such expression is significantly increased following sciatic nerve injury or dorsal root injury, particularly in astrocytes surrounding dorsal funiculus containing the central processes of the injured primary sensory neurons. The present invention has further demonstrated that Mts1 proteins administered extracellularly promote neurite outgrowth from neuronal cells. Based on these surprising findings, the present invention provides compositions and methods that are useful for the treatment of various neurological conditions characterized by death, degeneration or injury of neuronal cells.

Abstract: The present invention provides a complex of human growth hormone and zinc containing human growth hormone and zinc at a molar ratio of about 1:1.6 to about 1:2.4, and a sustained-release preparation which comprises the complex of human growth hormone and zinc and a biodegradable polymer and which has a high entrapment ratio of human growth hormone and exhibits a stable sustained-release suppressing the initial burst.

Abstract: An nNOS associated protein designated PIN-1 (Protein Inhibitor of nNOS) has been identified. It physically interacts with nNOS and inhibits its activity. Multiple lines of evidence indicate that PIN-1 is a regulator of nNOS: it is physiologically associated with nNOS, and it inhibits its catalytic activity. The extraordinary evolutionary conservation of PIN-1 and preliminary evidence that it interacts with multiple proteins, suggests that it may be a major biological regulatory protein influencing numerous physiological processes.

Abstract: Solid phase immunoassay for detecting specific inhibitors of proteolytic enzymes in biological fluids, which comprises: a) contacting a tubulin peptide covalently linked to a support with a solution containing a proteolytic activity together with a protease inhibitor, b) detecting the inhibitor activity against the selected proteases by contacting the support with a solution containing a labelled monoclonal antibody which specifically recognises the free end of the tubulin peptide linked to the support.

Abstract: The present invention provides reagents and assays for the quantification of hBNP in biological fluid samples such as plasma or serum. Antibodies are provided which are monospecific to epitopes comprising the amino acid sequences 5-13, 1-10 and 15-25 of hBNP. These antibodies, and peptide fragments containing these sequences, can be employed in the assays of the invention, which may be carried out in a sandwich format or a competition format.

Abstract: Nucleic acid compositions are provided that encode a family of mammalian proteins expressed in the retina and brain. Members of the gene family are genetically linked to various neurosensory defects, including cochlear degeneration, peripheral retinal degeneration and cone-rod retinal dystrophy. The nucleic acid compositions find use in identifying DNA sequences encoding homologous or related proteins; for production of the encoded protein; and in studying associated physiological pathways. In addition, modulation of the gene activity in vivo is used for prophylactic and therapeutic purposes, such as treatment of neurosensory defects, identification of retinal cells based on expression, and the like. The DNA is further used as a diagnostic for genetic predisposition to the linked neurosensory defect.

Abstract: The method of the invention for producing a composition for the sustained release of biologically active hGH includes dissolving a biocompatible polymer in a polymer solvent to form a polymer solution, dispersing particles of biologically active, metal cation-stabilized hGH in the polymer solution, and then solidifying the polymer to form a polymeric matrix containing a dispersion of said hGH particles.

Abstract: The invention provides a two new human DnaJ-like proteins (HSPJ1 or HSPJ2) and polynucleotides which identify and encode HSPJ1 or HSPJ2. The invention also provides expression vectors, host cells, agonists, antibodies and antagonists. The invention also provides methods for treating disorders associated with expression of HSPJ1 or HSPJ2.

Abstract: Neurotransmission by excitatory amino acids (EAAs) such as glutamate is mediated via membrane-bound surface receptors. DNA coding for one family of these receptors, of the kainate binding type of EAA receptors, has now been isolated and the receptor protein characterized. Herein described are recombinant cell lines which produce the EAA receptor as a heterologous membrane-bound product. Also described are related aspects of the invention, which are of commercial significance. Included is use of the cell lines as a tool for discovery of compounds which modulate EAA receptor simulation.

Abstract: A label-based assay is described, through modifications of substrate strure and derivatization of serum albumin, which can be used to determine type A proteolytic activity without separation of products.

Abstract: The present invention is directed to recombinant hosts expressing novel proteins associated with Alzheimer's Disease, neuroectodermal tumors, malignant astrocytomas, and glioblastomas. This invention is specifically directed to the recombinant hosts and vectors which contain the genes coding for the neuronal thread proteins. This invention is also directed to substantially pure neural thread protein, immunodiagnostic and molecular diagnostic methods to detect the presence of neural thread proteins, and the use of nucleic acid sequences which code for neural thread proteins in gene therapy.

Abstract: A substantially pure mammalian protein, hereinafter "zonulin", that is a physiological modulator of mammalian tight junctions is disclosed, as well as methods for the use of the same.

Abstract: A novel neurotrophic factor referred to as glial cell line-derived neurotrophic factor (GDNF) has been identified and isolated from serum free growth conditioned medium of B49 glioblastoma cells. Rat and human genes encoding GDNF have been cloned and sequenced. A gene encoding GDNF has been subcloned into a vector and the vector has been used to transform a host cell in order to produce biologically active GDNF in a recombinant DNA process. Antibodies to GDNF are disclosed, as well as methods for identifying members of the GDNF family of neurotrophic factors.

Abstract: The method of the invention for producing a composition for the sustained release of biologically active hGH includes dissolving a biocompatible polymer in a polymer solvent to form a polymer solution, dispersing particles of biologically active, metal cation-stabilized hGH in the polymer solution, and then solidifying the polymer to form a polymeric matrix containing a dispersion of said hGH particles.

Abstract: The present invention relates to the diagnosis of multiple sclerosis. More specifically, this invention relates to an assay for detecting antigen(s) associated with multiple sclerosis. The present invention also relates to the generation of hybridomas which produce monoclonal antibodies which are specific for the multiple sclerosis-associated antigens. The present invention's use is in diagnosing multiple sclerosis and in routine follow-up monitoring of multiple sclerosis patients as to disease progression or response to therapy.

Abstract: Disclosed are DNA and amino acid sequences for a novel polypeptide termed Neuritin which is expressed primarily in selected regions of the brain.

Abstract: A process for extraction of myelin basic protein from myelin containing tissue, such as central nervous system tissue, which process comprises the following steps:extraction of the myelin basic protein from myelin containing tissue with an organic solvent selected from the group consisting of chloroform and compounds having a polarity similar to that of chloroform;incubation of the organic phase in the presence of a lower aliphatic alcohol or propylene glycol;transfer of the myelin basic protein from the lower aliphatic alcohol/organic solvent mixture to an aqueous phase with the aid of hydrogen ions (protons); andrecovery of the purified myelin basic protein. The invention also relates to the product obtainable by the process.

Abstract: Methods of generating a rat having A.beta. deposits in the brain of the rat by injecting an amount of human A68 protein sufficient to result in formation of the deposits and subsequently examining the rat for the formation of the deposits are disclosed. Rats characterized by the presence of A.beta. deposits similar to those found in individuals with Alzheimer's disease are also disclosed. Methods of screening test compositions for prophylactic or therapeutic activity by generating a rat having A.beta. deposits in its brain, treating the animal with the test composition and examining the animal for therapeutic or prophylactic effectiveness are also disclosed.

Abstract: The present invention relates to nucleotide sequences of the Delta genes, and amino acid sequence of the encoded protein, fragments and derivatives which retain binding activity are also provided.

Abstract: The present invention provides a labelled .beta.-amyloid peptide or a labelled active fragment of .beta.-amyloid peptide and methods of using the labelled peptides to screen for agents which affect the deposition of the labelled peptide onto amyloid plaques in tissue samples evidencing the presence of Alzheimer's amyloidosis.

Abstract: Derivatives of the neurotrophic factors BDNF and NT-3 have been prepared by attachment of these polypeptides to a water soluble polymer, for instance, polyethylene glycol.

Abstract: The present invention relates to a purified non-neuronal activity-dependent neurotrophic factor (ADNF) protein that increase the survival of spinal cord neuron cells, cerebral cortical cells and hippocampal neuron cells which has a molecular weight of 16,000 to 18,000 Daltons as determined by sodium dodecyl sulfate polyacrylamide gel electrophoresis, and a basic pI of about 8.1.

Abstract: Novel ligands that bind Eph family receptors are identified, and methods for making the soluble ligands in biologically active form are described. cDNA clones encoding these novel proteins enable production of the recombinant proteins, which are useful to support neuronal and other receptor-bearing cell populations.

Abstract: Methods of identifying compounds capable of affecting binding of a SNAP-25, .alpha.-SNAP, n-sec1 or VAMP to syntaxin are disclosed. Compounds identified by such methods are useful for modulating vesicular release, such as release at neural synapses.

Abstract: The present invention provides an anti-N-CAM monoclonal antibody which enhances, rather than inhibits, neurite outgrowth both in vitro and in vivo. The antibody has positive regulatory effects on nerve cells of both the central and peripheral nervous systems, and is useful for enhancing neurite outgrowth in in vitro studies and for improving nerve regeneration and repair in vivo.

Abstract: This application describes a purified and isolated fragment of a nucleic acid molecule encoding an amyloid precursor mutein, wherein the fragment comprises a nucleic acid sequence encoding at least one marker and a nucleic acid sequence of about 419, about 475 or about 494 amino acid residues in which a portion thereof encodes a .beta.-amyloid protein domain. Also described is a method for screening for a compound which reduces the formation of .beta.-amyloid protein.

Abstract: A composition, and methods of forming and using said composition, for the sustained release of biologically active, stabilized human growth hormone (hGH). The sustained release composition of this invention comprises a polymeric matrix of a biocompatible polymer and particles of biologically active, stabilized hGH, wherein said particles are dispersed within the biocompatible polymer. The method of the invention for producing a composition for the sustained release of biologically active hGH, includes dissolving a biocompatible polymer in a polymer solvent to form a polymer solution, dispersing particles of biologically active, stabilized hGH in the polymer solution, and then solidifying the polymer to form a polymeric matrix containing a dispersion of said hGH particles. The method for using a composition of the invention is a method for providing a therapeutically effective blood level of biologically active, non-aggregated hGH in a subject for a sustained period.

Abstract: This application describes a purified and isolated fragment of a nucleic acid molecule encoding an amyloid precursor mutein, wherein the fragment comprises a nucleic acid sequence encoding at least one marker and a nucleic acid sequence of about 419, about 475 or about 494 amino acid residues in which a portion thereof encodes a .beta.-amyloid protein domain. Also described is a method for screening for a compound which reduces the formation of .beta.-amyloid protein.

Abstract: The present invention provides an anti-N-CAM monoclonal antibody which enhances, rather than inhibits, neurite outgrowth both in vitro and in vivo. The antibody has positive regulatory effects on nerve cells of both the central and peripheral nervous systems, and is useful for enhancing neurite outgrowth in in vitro studies and for improving nerve regeneration and repair in vivo.

Abstract: The present invention relates to nucleotide sequences of the human Notch and Delta genes, and amino acid sequences of their encoded proteins, as well as fragments thereof containing an antigenic determinant or which are functionally active. The invention is also directed to fragments (termed herein "adhesive fragments"), and the sequences thereof, of the proteins ("toporythmic proteins") encoded by toporythmic genes which mediate homotypic or heterotypic binding to toporythmic proteins. Toporythmic genes, as used herein, refers to the genes Notch, Delta, and Serrate, as well as other members of the Delta/Serrate family which may be identified, e.g., by the methods described herein. Analogs and derivatives of the adhesive fragments which retain binding activity are also provided. Antibodies to human Notch and to adhesive fragments are additionally provided.

Abstract: This invention provides a purified protein, having an apparent molecular weight of about 800 kDa, designated merosin. Also provided is an isolated nucleic acid sequence which encodes merosin. The invention further provides antibodies, vectors, and the expression of recombinant proteins by use of a host vector system. The invention also provides the use of merosin to promote neurite growth and for certain diagnostic applications.