Abstract: The invention provides compositions for increasing the clearance of protein aggregates, and pharmaceutical compositions comprising them, and methods for making and using them, including methods for accelerating protein aggregate clearance in the CNS, e.g., for treating diseases that are characterized by protein aggregation—including some degenerative neurological diseases such as Parkinson's disease. In one aspect, the compositions of the invention specifically target synuclein, beta-amyloid and/or tau protein aggregates, and the methods of the invention can be used to specifically prevent, reverse, slow or inhibit synuclein, beta-amyloid and/or tau protein aggregation. In alternative embodiments, the compositions and methods of the invention, are used to treat, prevent, reverse (partially or completely) or ameliorate (including slowing the progression of) degenerative neurological diseases related to or caused by protein aggregation, e.g., synuclein, beta-amyloid and/or tau protein aggregation.

Abstract: This invention relates to a vaccine for preventing or treating tautopathy, comprising a vector, as an active ingredient, comprising a nucleic acid encoding a mutant tau protein linked to a secretion signal sequence, wherein the vaccine is capable of inducing an antibody against an (optionally phosphorylated) tau protein in a subject in a more sustained manner compared with a case where the mutant tau protein is administered directly.

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: In its various embodiments, the invention provides myelin basic proteins and fragments of that interfere with the fibrillization of peptides implicated in the amyloidoses, especially the amyloid-b eta peptide associated with Alzheimer's disease (“AD”) and cerebral amyloid angiopathy (“CAA”). Some embodiments provide methods of identifying additional interfering fragments. Others provide methods of identifying substances that modulate the interference. Further embodiments provide methods of preventing amyloidoses, especially AD and CAA by administering myelin basic proteins or fragments thereof.

Abstract: A transformed soybean plant having a gene encoding a modified seed storage protein introduced therein, obtained by inserting a gene encoding an Alzheimer's disease vaccine to a variable region(s) of a gene encoding a wild-type seed storage protein, is produced, and said vaccine is produced and accumulated in the seeds thereof.

Abstract: The present invention provides peptide-based peroxidase inhibitors having the formula AA1-AA2-AA3, wherein AA1 is a positively charged, negatively charged or neutral amino acid, AA2 is a redox active amino acid, and AA3 is an amino acid possessing a reducing potential such that AA3 is capable of undergoing a redox reaction with a radical of amino acid AA2 or a retro or retro-inverso analog thereof. The result of such a combination is a highly effective inhibitor of peroxidase activity that has potent anti-inflammatory properties in widely diverse models of vascular disease and injury. Exemplary tripeptides effectively inhibit peroxidase mediated LDL oxidation, increase vasodilation in SCD mice, inhibit eosinophil infiltration and collagen deposition in asthma mice, inhibit acute lung injury, and decrease ischemic injury of the heart.

Abstract: New liposomes are described, comprising: (i) phosphatidic acid and/or cardiolipin; (ii) apolipoprotein E (ApoE) or derivatives thereof. The so modified liposomes, administered systemically, obtain a dramatic in-vivo reduction of the amyloid plaque in the central nervous system, allowing an effective treatment of neurodegenerative diseases, in particular Alzheimer's disease.

Abstract: In certain embodiments compositions are provided that comprise a pentapeptide comprising the formula: C1-X2-X3-X4-C5 where C1 and C5 are independently selected cysteines or cysteine analogues, or other amino acids with sidechains suitable for cyclization, where the cysteines or cysteine analogs are attached to each other by a linkage that does not comprise X2, X3, and X4; where X2, X3, and X4 are independently selected amino acids; and the peptide, when administered to a cell alters APP signaling and/or switches APP processing from aberrant to normal. The compositions mitigate amyloid plaque formation.

Abstract: The invention relates to compounds that can be used, in particular, as structural mimetics of proline-rich peptides and are correspondingly able to bond with proline-rich-motif binding domains (PRM domains) of proteins. The invention further relates to the use of these compounds as pharmaceutically active agents, as well as the use of the pharmaceutically active agents for the treatment of bacterial, neurodegenerative and tumor diseases.

Abstract: The object of the invention is based on inhibiting specific phosphorylation on Thr248 and/or Thr250 residues of human transcription factor E2F4 to inhibit somatic endoreduplication processes in postmitotic cells which may be associated with various pathological conditions. The invention covers all currently known methods for the specific inhibition of protein phosphorylation (including the expression of mutant forms of E2F4 without Thr residues phosphorylated by p38MAPK) or methods developed in the future that may be applied to Thr-248 and/or Thr-250 residues of human transcription factor E2F4.

Abstract: The invention provides human secreted proteins (SECP) and polynucleotides which identify and encode SECP. The invention also provides expression vectors, host cells, antibodies, agonists, and antagonists. The invention also provides methods for diagnosing, treating, or preventing disorders associated with aberrant expression of SECP.

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 reentry 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: 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: The present invention provides indane acetic acid and their derivatives and methods for the treating and/or preventing of cognitive disorders.

Abstract: A primary object of the present invention is to develop a compound that specifically inhibits the production of A? protein and serves as an active ingredient of a drug to treat and/or prevent Alzheimer's disease. This object can be achieved by a polypeptide having the amino acid sequence represented by any one of SEQ ID NOs: 1, 13, 14, and 22, that binds to the N-terminal region of ?CTF; a ?-secretase activity inhibitor containing the polypeptide; ?-secretase activity inhibitor; A? protein production inhibitor; and an agent for treating and/or preventing Alzheimer's disease.

Abstract: Disclosed herein is a method for stimulating axonal outgrowth of central nervous system (CNS) neurons comprising contacting the CNS neurons with an effective amount of NEP1-40 and inosine, to thereby stimulate axonal outgrowth. The method may further comprise contacting the CNS neurons with a cAMP modulator that increases the concentration of intracellular cAMP. Also disclosed is a method for treating a neurological disorder selected from the group consisting of traumatic brain injury, stroke, spinal cord injury, optic neuropathy, retinal nerve damage and optic nerve damage, in a patient in need thereof comprising administering an effective amount of NEP1-40 and inosine to the patient.

Abstract: A vaccine composition for prophylaxis and/or therapy of Alzheimer's disease, which comprises a fusion protein prepared by inserting a single or tandemly repeated multiple copies of amyloid ? antigenic peptide having 5 to 15 continuous amino acid residues derived from the N-terminus of amyloid ? peptide into a wild type seed storage protein.

Abstract: The present invention provides monoclonal antibodies which specifically recognize the shorter A? peptides obtained after cleavage of the APP protein mediated by ?-secretase, i.e. the A?-peptide fragments A?1-37, A?3-37, A?3p-37, A?1-37 and A?11p-37, and other like fragments ending at the 37th amino acid of APP, hereinafter also referred to as the A?x-37 peptides. It further provides hybridoma cells producing the monoclonal antibodies as well as methods for producing the antibodies and the hybridoma cells; and an immunoassay for an A?x-37 peptide by a competitive method or a sandwich method using the antibody of the present invention; and methods for measuring the level of A?x-37 peptides in a sample, such as a biological sample.

Abstract: The present invention describes peptides comprising phycocyanobilin (PCB), as well as the medical use of said peptides and that of PCB, due to the neuroprotector and/or neuroregenerative effects identified for them. Furthermore, pharmaceutical combinations of said peptides and of PCB with proteins or other peptides with synergic effect justify their use for ischemic or neurodegenerative CNS disease treatment.

Abstract: An isolated human cell is disclosed comprising at least one mesenchymal stem cell phenotype and secreting brain-derived neurotrophic factor (BDNF), wherein a basal secretion of the BDNF is at least five times greater than a basal secretion of the BDNF in a mesenchymal stem cell. Methods of generating same and uses of same are also disclosed.

Abstract: Described herein is the use of a visible near infrared (VNIR) hyperspectral imaging system as a non-invasive diagnostic tool for early detection of Alzheimer's disease (AD). Also described herein is the use of a VNIR hyperspectral imaging system in high throughput screening of potential therapeutics against AD.

Abstract: N-acylpeptide derivatives are described. Compositions comprising N-acylpeptide derivatives are therapeutically effective for topical or systemic administration to alleviate or improve conditions, disorders, diseases, symptoms or syndromes associated with tumors or cancers, immune, nervous, vascular, musculoskeletal, cutaneous system, or other tissues or systems in a subject.

Abstract: The present invention relates to certain chromane-like cyclic prenylflavonoids, in particular the compounds of formulae (I), (II) and (III) as described and defined herein, for use in the treatment or prevention of a neurological disorder, as well as their use in promoting neuronal differentiation, neurite outgrowth and neuroprotection.

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: The invention relates to agents and to pharmaceutical compositions for reducing the formation of amyloid and/or for promoting the disaggregation of amyloid proteins. The compositions may also be used to detect amyloid.

Abstract: Disclosed is a composition immunologically targeted to Alzheimer's disease (AD), the composition containing amine functionalized nanoparticles of Cerium oxide coated with polyethylene glycol and bearing an antibody specific for an amyloid-beta antigen associated with AD. The invention also includes a medication manufactured with the targeted nanoceria particles and methods of treatment by administering the targeted nanoceria particles to patients in need thereof.

Abstract: The present invention is related to the tripeptide (I)Lys-(d)Pro-(I)Thr (KdPT) or pharmaceutically acceptable salts thereof for therapeutic, prophylactic therapeutic or cosmetic treatment of a disease with increased apoptosis, wherein the treatment has an anti-apoptotic effect. The present invention is also related to the use of KdPT or pharmaceutically acceptable salts thereof for the manufacture of a pharmaceutical or cosmetic composition for an anti-apoptotic treatment of disorders that are related with increased apoptosis.

Abstract: Provided are fragments of human p97 (melanotransferrin) polypeptides having blood-brain barrier (BBB) transport activity, including variants and combinations thereof, conjugates comprising said p97 fragments, and related methods of use thereof, for instance, to facilitate delivery of therapeutic or diagnostic agents across the BBB.

Abstract: A method of treating loss of brain function in a patient comprising the steps of preparing a composition comprising a D peptide and a pharmaceutically acceptable carrier. The D peptide has the general structure: A-B-C-D-E-F-G-H in which A is Ala, or absent, B is Ser, Thr or absent, C is Ser, Thr or absent, D is Ser, Thr, Asn, Glu, Arg, Ile, Leu, E is Ser, Thr, Asp, Asn, F is Thr, Ser, Asn, Arg, Gln, Lys, Trp, G is Tyr, and H is Thr, Ser, Arg, Gly. All amino acids in the D peptide are the D stereoisomeric configuration. The peptide composition is administered in a therapeutically effective dose.

Abstract: Soluble Neuregulin-1 isoforms representing Posttranslational Neuregulin-1 modifications for reducing dopaminergic cell death.

Abstract: The present invention relates to compositions and methods for altering cell function. In particular, the present invention provides compositions comprising selenium (e.g., SEL-PLEX) and methods of using the same (e.g., as a therapeutic and/or prophylactic treatment for neurodegenerative disease). Additionally, the present invention demonstrates that specific forms of selenium (e.g., SEL-PLEX) possess the ability to alter expression of genes associated with disease and/or aging while other forms of selenium (e.g., selenomethionine) do not.

Abstract: Provided herein are peptides that exhibit ApoE biological activity, as well as compositions and pharmaceutical formulations that include the peptides. The peptides, compositions, and methods disclosed herein have broad applications as they can be used to treat a broad spectrum of injury, diseases, disorders, and clinical indications.

Abstract: Potent compounds having combined antioxidant, anti-inflammatory, anti-radiation and metal chelating properties are described. Short peptides having these properties, and methods and uses of such short peptides in clinical and cosmetic applications are described.

Abstract: The invention includes methods of neuroprotection, inducing release of neurotrophic factors, inhibiting the over-activation of innate immune cells, attenuating the toxin-induced death and/or damage of tissues, reducing inflammation, treating an inflammation-related condition, and inhibiting NADPH oxidase, that includes contacting or administering an effective amount of at least one compound of the invention that include: valproic acid, sodium butyrate, and salts thereof; opioid peptides; a peptide comprising the tripeptide GGF; and morphinans, such as naloxone, naltrexone, 3-hydroxy-morphinan and dextromethorphan.

Abstract: N-acyldipeptide derivatives are described. Compositions comprising the N-acyldipeptide derivatives are therapeutically effective for topical or systemic administration to alleviate or improve conditions, disorders, diseases, symptoms or syndromes associated with a tumor, cancer, immune, nervous, vascular, musculoskeletal or cutaneous system, or other tissue or system in a subject.

Abstract: The present invention provides compounds, compositions and methods for treatment and/or prevention of neurodegenerative diseases, including but not limited to autoimmune diseases, such as multiple sclerosis, in which demyelination, (the loss of the myelin sheath that insulates the nerves) is an associated or causative feature. The data provided demonstrate the utility of the compounds and compositions according to this invention to promote oligodendrogenesis and myelination or remyelination.

Abstract: In sporadic Alzheimer's disease, neurofibrillary lesion formation is preceded by extensive post-translational modification of the microtubule associated protein tau. Immunoassays have been developed recently that detect tau in biological specimens, thus providing a means for pre-mortem diagnosis of Alzheimer's disease, which has remained elusive. These assays have been improved by the analysis of relevant post-translational modifications, such as phosphorylation, however opportunity for improvement remains. The present invention addresses this issue by disclosing synthetic methylated peptides derived from the tau protein of paired helical filaments and non-diseased control brain. Alzheimer's disease specificity is provided by the presence or absence of methyl moieties on lysine residues and differences between mono-, di-, and tri-methylation.

Abstract: Provided herein are genetic variants associated with development of a condition of interest (e.g., Alzheimer's disease). Methods of treatment with an active agent (e.g., with a particular active agent and/or at an earlier age) is also provided, upon detecting a genetic variant described herein. In some embodiments, the genetic variant is a deletion/insertion polymorphism (DIP) of the TOMM40 gene.

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 compositions and methods to administer compositions comprising cupredoxin and/or cytochrome and/or variants, derivatives, truncations and structural equivalents of cupredoxin and cytochrome to treat and/or prevent two or more conditions in a mammalian cell. The invention also relates to compositions and methods to administer compositions comprising cupredoxin and/or cytochrome and/or variants, derivatives, truncations and structural equivalents of cupredoxin and cytochrome to concurrently treat and/or prevent two or more conditions in a patient such as HIV, cancer, malaria and inappropriate angiogenesis.

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: Provided herein are methods of promoting parkin activity in a subject, comprising: selecting a subject with a disorder associated with decreased Parkin activity; and administering to the subject an effective amount of a composition that increases parkin activity, wherein the composition is an inhibitor of a deubiquitinating enzyme.

Abstract: The invention provides ultra-small peptide inhibitors that are capable of preventing amyloid formation/amyloidosis.

Abstract: Methods and compositions are provided for treatment of neurodegenerative diseases in which there is accumulation of misfolded and/or aggregated proteins, excluding prion diseases. In particular, the invention relates to treatment of the neurodegenerative diseases Huntington's disease (HD), Alzheimer's disease (AD) or Parkinson's disease (PD), by administration of an agent selected from the group consisting of (i) Copolymer 1, (ii) a Copolymer 1-related peptide, (iii) a Copolymer 1-related polypeptide, and (iv) T cells activated with (i), (ii) or (iii).

Abstract: The invention provides polypeptides comprising a complement factor B analog. The invention also provides various complement factor B analogs including complement factor B analogs comprising a mutation of a free cysteine amino acid and related methods, nucleic acids and vectors. These complement factor B analogs and related methods, nucleic acids and vectors can be used to modulate a complement pathway or for the study and/or treatment of various conditions or diseases related to a complement pathway.

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 invention provides peptide inhibitors of BACE1 that bind to the active site in a noncanonical fashion, and methods of use thereof.

Abstract: The present invention relates to a neurotrophic peptide having an amino acid sequence of VGDGGLFEKKL (SEQ ID NO: 1) and alternatively comprising an adamantyl group at the C-and/or N-terminal end. The neurotrophic peptide can rescue cognition, correct impairments in neural cell proliferation and synaptic plasticity, and thus address the cognitive defects associated with Alzheimer's disease.

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: 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.