Abstract: The invention relates to cyclic peptide agonists that bind to the mu (morphine) opioid receptor and their use in the treatment of acute and/or chronic pain. Embodiments of the invention are directed to cyclic pentapeptide and hexapeptide analogs of endomorphin that have (i) a carboxy-terminal extension with an amidated hydrophilic amino acid and (ii) a substitution in amino acid position 2. These peptide analogs exhibit decreased tolerance relative to morphine, increased solubility compared to similar tetrapeptide analogs, while maintaining favorable or improved therapeutic ratios of analgesia to side effects.

Abstract: Use of a GPR54 agonist or antagonist for the treatment of a disease or disorder presenting behavioral abnormalities associated with impairment of sensory gating function, and/or for treatment of depression, and/or for improving cognitive function is disclosed. In particular, the invention relates to the use of kisspeptin or a peptide thereof for the treatment of schizophrenia.

Abstract: A method of treatment for treating, preventing, inhibiting or reducing tissue deterioration, injury or damage due to a neuro-, muscular- or neuro-muscular-degenerative disease, or for restoring tissue adversely affected by said disease, in a subject, includes administering to a subject in need of such treatment an effective amount of a composition including a peptide agent including amino acid sequence LKKTET or LKKTNT, a conservative variant thereof, or a peptide agent that stimulates production of an LKKTET or LKKTNT peptide, or a conservative variant thereof, in the tissue.

Abstract: Novel therapeutic compounds for use against Huntington's disease. More especially, an isolated peptide of size less than 100 amino acids and containing: a first sequence having at least 80% identity with sequence AASSG (SEQ ID NO: 1), or a second sequence having at least 80% identity with sequence XAGXDXXTEXPXS (SEQ ID NO: 2), where X designates any amino acid. The use of an isolated peptide of size less than 200 amino acids and containing the sequence(s) defined above, as a drug is also described.

Abstract: Provided are materials and methods for the prevention and treatment of Juvenile Neuronal Ceroid Lipofuscinosis comprising administration of an effective amount of at least one of a hemi-channel inhibitor or a phosphodiesterase-4 inhibitor. In some embodiments, the methods comprise administration of an effective amount of each of a hemi-channel inhibitor and a phosphodiesterase-4 inhibitor. Also provided are pharmaceutical compositions comprising a hemi-channel inhibitor or a phosphodiesterase-4 inhibitor, as well as kits comprising at least one effective dose of a hemi-channel inhibitor or a phosphodiesterase-4 inhibitor or a combination of both.

Abstract: A peptide comprising a unit of formula (I) and having a molecular weight of less than 2000 wherein each X is independently an organic group, e.g. a C1-6 alkyl or C1-6 alkenyl group, preferably —CH2—CH?CH2, or the two X groups taken together can form a covalent or non-covalent link between the two O groups, preferably a C1-10 saturated or unsaturated carbon chain optionally interrupted by one or more heteroatoms selected from O, S, N, P, or Si, especially a C3-10 carbon chain or one X represents an azido group and the other an C2-6-alkynyl group; both Z's are the same and are O or S; each Y is independently C, CH, CH2, N or NH; R1 is H or C1-6 alkyl; R2 is H or C1-6 alkyl; R5 is a C1-6 alkyl group, preferably isopropyl; or a salt, ester or prodrug thereof.

Abstract: A neuronal differentiation inducer provided by the present invention contains an artificially synthesized peptide which includes an amino acid sequence constituting a signal peptide in amyloid precursor protein (APP), or a partial sequence of the amino acid sequence constituting this signal peptide.

Abstract: The present invention provides a novel class of macrocyclic compounds, which are useful as cysteine protease inhibitors. Also provided are novel intermediates and methods of preparing the compounds. The invention also provides pharmaceutical compositions comprising the compounds. The compounds and compositions are useful in methods of treating or preventing one or more diseases associated with cysteine protease activity, particularly those associated with calpain activity.

Abstract: The present invention compositions and methods of using at least a portions of an isolated and purified ?-crystallin polypeptide that includes one or more ?-pleated sheets and that prevents neurotoxicity and amyloidogenesis.

Abstract: The invention provides a method for treating a medical condition, disease, or disorder mediated by a misfolded form of superoxide dismutase (SOD) in a subject in need of treatment. The method optionally comprises administering to the subject a composition comprising a pharmaceutically acceptable vehicle and an agent selected from (1) an exogenous antibody or fragment thereof that binds selectively to the misfolded form of SOD, and/or (2) an immunogen that elicits production of an endogenous antibody that binds selectively to the misfolded form of SOD, and/or (3) a nucleic acid sequence encoding (1) or (2).

Abstract: The present application relates to the use of a pertussis toxin, and its derivatives, analogs, salts and pharmaceutical equivalents. In one embodiment, the invention provides a method of treating an autoimmune disease by administering pertussis toxin to the individual. In another embodiment, the autoimmune disease is multiple sclerosis. In another embodiment, the invention provides a method of treating a neurodegenerative disease such as Alzheimer's disease or Parkinson's disease by administering pertussis toxin, or a derivative, analog, salt or pharmaceutical equivalent.

Abstract: This disclosure features modified release pharmaceutical formulations (e.g., extended release pharmaceutical formulations; e.g., solid dosage forms, e.g., tablets) that are useful for the oral administration of oprozomib, or a pharmaceutically acceptable salt thereof, to a human or animal subject as well as methods of making and using the formulations.

Abstract: The invention is directed to methods of treatment of Alzheimer's disease and other tauopathies, via the administration of antibodies having specificity to abnormal forms of tau protein, the antibodies showing no binding and/or reactivity to a normal tau protein and being administered under conditions and in amounts effective to prevent or treat Alzheimer's disease or other tauopathies. In certain embodiments, the antibodies are selective for soluble truncated tau protein truncated at (i) its C-terminus after the glutamic acid residue Glu391, or (ii) at the aspartic acid residue Asp421, or (iii) at its N-terminus at the aspartic acid residue Asp13, or (iv) a combination of (i)-(iii). Further aspects of the invention are directed to the administration of an immunogen comprising an abnormal tau, preferably a soluble truncated tau.

Abstract: Methods, uses, agents and compositions useful for the prevention, treatment and/or diagnosis of neuroinflammatory conditions such as multiple sclerosis and spinal cord injury based on the modulation of nerve injury-induced protein-1 (Ninjurin-1) are disclosed.

Abstract: Methods, compounds, pharmaceutical compositions and kits are described for treating or preventing amyloid-related disease.

Abstract: The disclosure relates, at least in part, to methods of treating autism in a patient in need thereof by administering an effective amount of a disclosed compound, e.g., a NMDA receptor glycine site partial agonist.

Abstract: Template-fixed ?-hairpin peptidomimetics of the general formula wherein Z is a template-fixed chain of 4 ?-amino acid residues which, depending on their positions in the chain (counted starting from the N-terminal amino acid) are Gly, or of certain types which, as the remaining symbols in the above formula, are defined in the description and the claims, and salts thereof, have the property to agonize or to antagonize GPCR receptors such as CXCR3, urotensin and CCR10. They can be used as medicaments to treat or prevent diseases such as cardiovascular disorders, dermatological disorders, endocrine system and hormone disorders, metabolic diseases, inflammatory diseases, neurological diseases, respiratory diseases, haematological diseases and cancer. These ?-hairpin peptidomimetics can be manufactured by a process which is based on a mixed solid- and solution phase synthetic strategy.

Abstract: Compounds are provided having inter alia good duration of action, high potency and/or convenient dosing regimens including oral administration. The compounds are engineered polypeptides which incorporate an albumin binding domain in combination with one or more biologically active polypeptides. Also provided are pharmaceutical compositions and methods of treatment for diseases and disorders including obesity and overweight, diabetes, dyslipidemia, hyperlipidemia, Alzheimer's disease, fatty liver disease, short bowel syndrome, Parkinson's disease, cardiovascular disease, and other and disorders of the central nervous system.

Abstract: Antibodies selective for pathological tau dimers and/or prefibrillar pathological tau oligomers, immunogenic peptides and epitopes of these antibodies, hydridomas producing these antibodies, uses of these antibodies, immunogenic peptides and epitopes in preparation of pharmaceutical compositions for the treatment of tauopathies, and uses of these antibodies, immunogenic peptides, epitopes and pharmaceutical compositions in the treatment of tauopathies are described. Also described are uses of these antibodies, immunogenic peptides, epitopes in diagnosis and monitoring of tauopathies.

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

Abstract: Use of an isolated peptide comprising an amino acid sequence being no more than 25 amino acids in length, the amino acid sequence comprising at least one aspartate or a homolog thereof, the peptide having an Insulin-Degrading Enzyme (IDE) inhibitory activity, for the manufacture of a medicament identified for treating a disease selected from the group consisting of diabetes, obesity, hyperglycemia, retinal damage, renal failure, nerve damage, microvascular damage and varicella-zoster virus (VZV) infection is disclosed.

Abstract: The present invention provides methods of treating or preventing a substance-related disorder using selective delta opioid receptor-1 (DOP-R1) agonists, delta opioid receptor-2 (DOP-R2) antagonists, and/or mu opioid receptor (MOP-R) antagonists, or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof. The methods provided herein further comprise administering a therapeutically effective amount of a combination of a DOP-R1 agonist and a DOP-R2 antagonist. The methods also comprise administering a therapeutically effective amount of a combination of a DOP-R1 agonist and an MOP-R antagonist. The methods provided herein further comprise administering a therapeutically effective amount of a combination of a DOP-R1 agonist and a DOP-R2 antagonist and a MOP-R antagonist. The invention also relates to compositions containing the same. The invention also relates to methods of determining delta opioid receptor specificity of candidate agents.

Abstract: A method of stimulating neuronal growth or repair comprising exposing a target neuron or neuronal area to a solution of the metallothionein isoform MT-IIA.

Abstract: The present invention relates to methods for modulating, i.e. increasing or decreasing, the length and/or the complexity of the dendrites of a neuronal cell by influencing the amount of vascular endothelial growth factor D (VEGFD)-related signaling. The present invention further relates to methods for treating age- and/or disease-related cognitive dysfunctions, or for impairing the memory of a subject. Finally, the present invention relates to recombinant VEGFD (rVEGFD) for use in the treatment of age- and/or disease-related cognitive dysfunctions.

Abstract: Small molecule, peptidic hepatocyte growth factors mimics, which act as both mimetics and antagonists, have been generated. These molecules have been shown or predicted to have therapeutic potential for numerous pathologies including dementia, Alzheimer's disease, Parkinson's disease, amyotrphic lateral sclerosis, and other neurodegenerative diseases, spinal cord injury, traumatic brain injury, diabetes and metabolic syndrome, cancer, and defective wound healing.

Abstract: The invention relates to novel pharmaceutically-useful peptides, in particular cyclic peptides that are agonists of the AngII type 2 receptor (AT2 receptor). The invention further relates to the use of such peptides as medicaments, to pharmaceutical compositions containing them, and to their production.

Abstract: There is provided a new use of protein hydrolysates and peptide derived from seahorses for preventing or treating a neurodegenerative disease, and more particularly a composition and health functional foods for preventing or treating a neurodegenerative disease including seahorse protein hydrolysates or peptide isolated and purified from the same as an effective component.

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 provides methods of treating stroke and related conditions exacerbated by fever and/or hyperglycemia by administering peptides or peptidomimetics that inhibit binding of NMDAR 2B to PSD-95 to a patient.

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 are provided for the treatment of subjects with cognitive or neuropsychiatric impairment induced by substance addiction and for increasing cognitive function in a subject with substance addiction. In some embodiments, the methods include administering to the subject a therapeutically effective amount of a major histocompatibility complex (MHC) molecule including covalently linked first, second, and third domains; wherein the first domain is an MHC class II ?1 domain and the second domain is an MHC class II ?1 domain; or wherein the first domain is an MHC class I ?1 domain and the second domain is an MHC class I ?2 domain; and wherein the third domain is covalently linked to the first domain and comprises an antigen of the central or peripheral nervous system.

Abstract: The present invention provides methods for guiding preservation of neurons or nerves during surgery by administering a fluorescently-labeled peptide or aptamer that specifically binds to the neurons or nerves. The invention further provides targeting molecules of fluorescently-labeled peptides or aptamers that specifically bind to neurons or nerves and for compositions thereof.

Abstract: The invention relates to polypeptides comprising an amino acid sequence which is an analogue of human amylin, pharmaceutical compositions comprising these polypeptides, and these polypeptides for use as medicaments.

Abstract: The present invention relates to uses of a peptide comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2, analogues and derivatives thereof, for the treatment of neurodegenerative diseases, such as amyotrophic lateral sclerosis (ALS). The present invention further provides a method for assessing responsiveness to treatment with the peptide of the invention. In addition, the present invention relates to prognosis of ALS progression, using Akt and phosphorylated Akt as biomarkers.

Abstract: Template-fixed ?-hairpin peptidomimetics of the general formula wherein Z is a template-fixed chain of 12 ?-amino acid residues which, depending on their positions in the chain (counted starting from the N-terminal amino acid) are Gly, or Pro, or of certain types which, as the remaining symbols in the above formula, are defined in the description and the claims, and salts thereof, have the property to selectively inhibit the growth of or to kill microorganisms such as Pseudomonas aeruginosa. They can be used as disinfectants for foodstuffs, cosmetics, medicaments or other nutrient-containing materials, or as medicaments to treat or prevent infections. These ?-hairpin peptidomimetics can be manufactured by processes which are based on a mixed solid- and solution phase synthetic strategy.

Abstract: The present invention provides improved formulations of botulinum toxin that increase delivery of the botulinum toxin to neural and associated tissues and exhibit a higher specific neurotoxicity and higher potency (in LD50 Units) than available formulations of botulinum toxins. These improved formulations enable physicians to treat a wide variety of pathological conditions with a lower toxin load that reduces the risk of inducing an immune response against the toxin and its associated proteins that may ultimately lead to the development of toxin resistance. These benefits are particularly important in the treatment of conditions that require high-dose or chronic administration of botulinum toxin. Additionally, the decreased in LD50 Unit doses of inventive formulations allows for controlled administration limits diffusion. The present invention also provides methods of treating neuromuscular diseases and pain, using low-dose botulinum toxin.

Abstract: The present disclosure provides methods for reducing axonal and/or synaptic degradation in neurons by modulating sterile ?/Armadillo/Toll-Interleukin receptor homology domain protein (SARM) activity and/or expression.

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

Abstract: The invention refers to agents for the preventive therapy after acute stroke, in particular having the aim to prevent infections after stroke. The agents inventively employed in pharmaceutical preparations are anti-infective agents and/or immunomodulating agents, e.g. cytokines and/or inhibitors of the SNS.

Abstract: This invention discloses CN2097-like compositions that facilitate the induction of long-term potentiation (LTP). In one embodiment the method comprises inducing long-term potentiation in a subject by the method of administering a therapeutically effective dose of a CN2097-like compound.

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: The present invention describes blood cells chemically coupled with immunodominant myelin peptides and their use in the treatment of Multiple Sclerosis.

Abstract: Methods and therapeutic agents are disclosed for treating neurodegenerative disorders by depletion of CD8 positive T cells by using antibodies, FAb fragments of antibodies or similar agents that sequester, neutralize or deplete the CD8+ cytotoxic T cells.

Abstract: A method of detecting MSDX Complex-1, the method introducing a first antibody to a sample to create an antibody-sample mixture, wherein the first antibody is specific for one of fibrinogen, fibronectin, or fibulin-1, the first antibody having a label molecule; providing a well coated with a second antibody, the second antibody is specific for one of fibrinogen, fibronectin, or fibulin-1; introducing the antibody-sample mixture to the well; and introducing a substrate to the antibody-sample mixture in the well, wherein the label molecule and the substrate interact to provide a signal, wherein when the signal is detected then MSDX Complex-1 is detected.

Abstract: The present invention discloses novel peptides derived from the IL-1 receptor antagonist protein (IL1 RA), capable of binding to the cell surface IL-1 receptor 1 (IL1 R1) and interfere with the binding of IL-1 to IL1 R1. This binding thus effectively antagonises the inflammatory effects of IL-1, such as by reducing TNF-alpha secretion from macrophages. This is of potential use as an anti-inflammatory factor throughout the human body, including the central nervous system. The use of said peptides as anti-inflammatory agents for treatment of pathological conditions wherein IL-1 plays a prominent role, such as inflammatory conditions of the body and the central nervous system, is thus an aspect of the present invention.

Abstract: Provided are compositions and methods for the treatment of Krabbe and other neurodegenerative diseases associated with psychosine (and/or other storage material)—mediated axonal degeneration. Compositions and methods employ one or more inhibitor(s) of (1) a phosphotransferase activity of one or more kinase(s) such as CDK5, P38, jnk, src, CK2, PKC, GSK3? and ?; (2) a phosphotransferase activity of one or more phosphatase(s) such as PP1 and PP2; (3) a caspase/calpain activity of one or more caspases such as caspase 3 and calpains such as calpain 1 and 2; and/or (4) a sodium/calcium exchange protein such as NCX1. Inhibitors include small molecules (e.g., the GSK3? inhibitor L803 and the NCX1 inhibitor flecainide) and siRNA molecules that downmodulate cellular levels of one or more mRNA, such as PP1 mRNA. Inhibitors disclosed can cross the blood-brain barrier and, thus, are available to the CNS and effective in reducing psychosine-mediated axonal degeneration.

Abstract: A nasal delivery device for and method of delivering a substance, preferably comprising oxytocin, non-peptide agonists thereof and antagonists thereof, preferably as one of a liquid, as a suspension or solution, or a powder to the nasal airway of a subject, preferably the posterior region of the nasal airway, and preferably the upper posterior region of the nasal airway which includes the olfactory bulb and the trigeminal nerve, and preferably in the treatment of neurological conditions and disorders.

Abstract: The present invention relates to methods for preventing or treating neurological diseases, particularly brain diseases, and improving cognitive functions using a composition comprising stanniocalcin 2 as an active ingredient.

Abstract: The present invention relates to novel polymer conjugates of polypeptide variants of the HMGB1 high affinity binding domain Box-A (HMGB1 Box-A) or of a biologically active fragment of HMGB1 Box-A. Further, the invention relates to novel polymer conjugates of polypeptide variants of the HMGB1 high affinity binding domain Box-A (HMGB1 Box-A). Moreover, the present invention concerns the use of said polymer conjugates of polypeptide molecules of HMGB1 Box-A to diagnose, prevent, alleviate and/or treat pathologies associated with extracellular HMGB1 and/or associated with an increased expression of RAGE.

Abstract: One aspect of the present disclosure relates to a method for modulating uterine function in a mammal. One step of the method includes placing a therapy delivery device into direct contact with a spinal cord target associated with uterine function. Next, the therapy delivery device is activated to deliver a therapy signal to the spinal cord target in an amount and for a time sufficient to effect a change in sympathetic and/or parasympathetic activity in the mammal and thereby modulate uterine function.