Abstract: This invention describes an ICE inhibitor prodrug (I) having good bioavailability. Compound I is useful for treating IL-1 mediated diseases such as rheumatoid arthritis, inflammatory bowel disease, Crohn's disease, ulcerative colitis, inflammatory peritonitis, septic shock, pancreatitis, traumatic brain injury, organ transplant rejection, osteoarthritis, asthma, psoriasis, Alzheimer's disease, myocardial infarction, congestive heart failure, Huntington's disease, atherosclerosis, atopic dermatitis, leukemias and related disorders, myelodysplastic syndrome, uveitis or multiple myeloma.

Abstract: Small molecule inhibitors of AGBL2 are provided, as well as methods of using the inhibitors to treat or prevent cancer and neurologic disorders.

Abstract: The present invention is related to methods and compositions for the therapeutic and diagnostic use in the treatment of diseases and disorders which are caused by or associated with amyloid or amyloid-like proteins including amyloidosis. In particular, the present invention provides novel methods and compositions for eliciting a highly specific and highly effective immune response in an organism, but particularly within an animal, particularly a mammal or a human, which is capable of preventing or alleviating amyloidosis, or the symptoms associated with amyloidosis, a group of diseases and disorders associated with amyloid plaque formation including secondary amyloidosis and age-related amyloidosis including, but not limited to, neurological disorders such as Alzheimer's Disease (AD), including diseases or conditions characterized by a loss of cognitive memory capacity such as, for example, mild cognitive impairment (MCI).

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

Abstract: The present invention relates to novel variants of human glial cell-derived neurotrophic factor (GDNF) and methods for their use.

Abstract: The present invention relates to linker molecules that readily conjugate cellular recognition ligand at one end and drug payload at the other, and are useful in treating or preventing cancer, an autoimmune disease, an inflammatory condition, a central nervous system disorder or an infection.

Abstract: The present invention is directed to methods, kits and compositions for preventing or treating age-related conditions or metabolic disorders. The Klotho fusion polypeptides of the invention include at least a Klotho protein or an active fragment thereof. In one embodiment, the fusion polypeptide comprises a Klotho polypeptide, a FGF (such as FGF23) and (optionally) a modified Fc fragment. The Fc fragment can, for example, have decreased binding to Fc-gamma-receptor and increased serum half-life. The Klotho fusion proteins are useful in the treatment and prevention of a variety of age-related conditions and metabolic disorders. In another embodiment, the fusion polypeptide comprises a FGF (such as FGF23) and a modified Fc fragment.

Abstract: The present invention derives from the finding that increased levels of Toll like receptor 4 (TLR4) is associated with liver failure and renal dysfunction and/or brain dysfunction and that by decreasing TLR4 levels in vivo, the kidney and brain consequences of liver disease that are precipitated by superimposed infection or inflammation may be reduced. Accordingly, the invention provides TLR4 antagonists for use in a method of treating an individual suffering from liver disease presenting with renal or brain dysfunction.

Abstract: The use of flagellin and flagellin related polypeptides for reducing cancer treatment side effects in mammals is described.

Abstract: The present invention relates to a cyclosporine emulsion containing: i) a cyclosporine ii) a natural oil (long chain triglyceride) iii) a phosphatidylcholine, iv) glycerol, v) a pharmaceutically tolerable alkali salt of a free fatty acid, vi) a medium chain triglyceride-oil vii) optionally, hydrochloric acid or sodium hydroxide for pH adjustment viii) water.

Abstract: A method for selection and treatment of externally caused migraine headache, the method includes identifying a patient group having chronic migraine headache; determining the identified patient group, a specific patient with a post traumatic migraine headache; and administering to the selected patient by injection of a therapeutically effective amount of an invertebrate presynaptic neurotoxin in a pharmaceutically safe form to the selected patient's head or upper neck; administration preferably being on the sites of the trigeminal cervical system, enabling axonal transport of the neurotoxin from distal to central sites; and the administration preferably comprising extramuscular injection of the neurotoxin of suitable dilution (a) over the aponeurotic fascia to enable the neurotoxin to diffuse into distal sensory nerves, in order to concentrate the neurotoxin over the occipital-parietal-frontal head region, or (b) intra-orally, in a foramina of the sphenopalatine ganglion for enabling diffusion of the neurotox

Abstract: The present invention is directed to the use of compounds of the formula: for treating pain, in particular neuropathic pain, bipolar disease and migraine headaches.

Abstract: The present invention relates to potent compounds having combined antioxidant, anti-inflammatory, anti-radiation and metal chelating properties. Specifically, the present invention relates to short peptides having these properties, and to methods and uses of such short peptides in clinical and cosmetic applications.

Abstract: The present invention relates to compounds of the formula (I) and in particular medicaments comprising at least one compound of the formula (I) for use in the treatment and/or prophylaxis of physiological and/or pathophysiological states in the triggering of which cathepsin D is involved, in particular for use in the treatment and/or prophylaxis of arthrosis, traumatic cartilage injuries, arthritis, pain, allodynia or hyperalgesia.

Abstract: The present invention relates to a neurotrophic peptide having an amino acid sequence of VGDGGLFEKKL (SEQ ID NO:1), EDQQVHFTPTEG (SEQ ID NO:2) or IPENEADGMPATV (SEQ ID NO:3), and comprising an adamantyl group at the C- and/or N-terminal end.

Abstract: The present invention relates to a new compound useful as a modulator of melanocortin receptors. In particular, the present invention relates to a compound WS727713, a process for production of the compound by culturing, in a culture medium, a WS727713-producing strain belonging to Pseudonocardia and recovering the compound from a culture broth, a pharmaceutical composition containing the compound, and uses of the compound.

Abstract: This invention is intended to discover a peptide that induces production of an antibody specific for an abnormal amyloid ? peptide from mimic peptides of the amyloid ? peptide and to utilize the same as a vaccine or immunogen. This invention relates to a pharmaceutical composition containing a peptide consisting of 8 to 30 amino acid residues, wherein the peptide comprises at least one of an amino acid sequence represented by formula (I): Tyr-Gly-Thr-Lys-Pro-Trp-Met (SEQ ID NO: 28) (I), and an amino acid sequence represented by formula (II): Leu-Asp-Ile-Phe-Ala-Pro-Ile (SEQ ID NO: 29) (II); or a conjugate of such peptide and a carrier.

Abstract: The invention relates to compositions and methods to confer protection on neurons. Peptides derived from the NAPVSIPQ (SEQ ID NO:4) peptide and including branched amino acids, such as alpha-aminoisobutyric acid, are included. Also included are methods of preventing and treating neurodegenerative disorders and damage caused by neurotoxic substances.

Abstract: Novel peptide inhibitors of GSK-3, compositions containing same and uses thereof are disclosed. The novel peptide inhibitors are substrate-competitive inhibitors and have an amino acid sequence designed so as to bind to a defined binding site subunit in GSK-3.

Abstract: The invention relates to novel benzodiazepine derivatives with antiproliferative activity and more specifically to novel benzodiazepines of formula (I) and (II), in which the diazepine ring (B) is fused with a heterocyclic ring (CD), wherein the heterocyclic ring is bicyclic or a compound of formula (III), in which the diazepine ring (B) is fused with a heterocyclic ring (C), wherein the heterocyclic ring is monocyclic. The invention provides cytotoxic dimers of these compounds. The invention also provides conjugates of the monomers and the dimers. The invention further provides compositions and methods useful for inhibiting abnormal cell growth or treating a proliferative disorder in a mammal using the compounds or conjugates of the invention. The invention further relates to methods of using the compounds or conjugates for in vitro, in situ, and in vivo diagnosis or treatment of mammalian cells, or associated pathological conditions.

Abstract: Disclosed herein are novel peptide linkers and polypeptide compositions comprising the linkers (e.g., chimeric polypeptides) and methods of using the polypeptide compositions. The compositions and methods are particularly useful for targeting/delivering a polypeptide or protein of interest (e.g., a therapeutic polypeptide) to a cell, tissue or organ of interest in order to treat various diseases or disorders (e.g., lysosomal storage disorders).

Abstract: Methods and materials are provided for the production of glycosylated peptides that exhibit high affinity and specificity for delta opioid receptors. The methods and materials of the present invention may be used for treatment of conditions involving pain, such as acute pain and nociceptic pain, neuralgia and myalgia.

Abstract: In one aspect, the invention provides a method of screening a human subject to determine if said subject has a genetic predisposition to develop, or is suffering from Facioscapulohumeral Dystrophy (FSHD), said method comprising: (a) providing a biological sample comprising genomic DNA from the subject; and (b) analyzing the portion of the genomic DNA in the sample corresponding to the distal D4Z4-pLAM region on chromosome 4 and determining the presence or absence of a polymorphism resulting in a functional polyadenylation sequence operationally linked to exon 3 of the DUX4 gene, wherein a determination of the absence of a functional polyadenylation sequence operationally linked to exon 3 of the DUX4 gene indicates that the subject does not have a genetic predisposition to develop, and is not suffering from FSHD, and/or wherein a determination of the presence of a functional polyadenylation sequence operationally linked to exon 3 of the DUX4 gene indicates that the subject has a genetic predisposition to devel

Abstract: The present invention includes a treating step of treating neuronal growth cone with a regulatory factor to regulate macropinocytosis caused by a repulsive axon guidance molecule. The present invention can provide a new neuronal axon elongation regulating method etc.

Abstract: Methods and pharmaceutical compositions for providing neuroprotection to the animal central nervous system against the effects of ischemia, and neurodegeneration. Patients at risk for certain diseases or disorders that are associated with cerebral ischemia may benefit, e.g., those at risk for Alzheimer's disease, Parkinson's disease, Wilson's disease or stroke or those patients having head or spinal cord injury. Patients undergoing certain medical procedures that may result in ischemia may also benefit. Initially, the possibility of ischemia or neurodegeneration is recognized. Intranasal therapeutic agents are administered to the upper third of the nasal cavity to bypass the blood-brain barrier and access the central nervous system directly to avoid unwanted and potentially lethal side effects. Therapeutic agents include those substances that interact with iron and/or copper such as iron chelators and copper chelators. A particular example of such therapeutic agents is the iron chelator deferoxamine (DFO).

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 invention herein related to methods and compositions for treating nervous system disorders. The methods comprise administration of antibodies directed towards peptides that bind to receptors important in disease progression, thus attenuating the disease.

Abstract: A delivery system. The delivery system includes a carrier or an active compound and a glutathione or a glutathione derivative grafted thereon. The invention also provides a compound including a moiety comprising a vitamin E derivative or a phospholipid derivative, a polyethylene glycol (PEG) or a polyethylene glycol derivative bonded thereto, and a glutathione (GSH) or a glutathione derivative bonded to the polyethylene glycol or the polyethylene glycol derivative.

Abstract: Provided are a composition for improving the brain function, which can be orally taken at a low dose, and a method therefor. The composition for improving the brain function contains, as the active ingredient, X-Pro-Pro-Leu-Thr-Gln-Thr-Pro-Val-Val-Val-Pro-Pro-Phe-Leu-Gln-Pro-Glu-Y (wherein X is nil or represents Ile or Asn-Ile; and Y is nil or represents Val-Met), X-Val-Val-Val-Pro-Pro-Phe-Leu-Gln-Pro-Glu-Y (wherein X is abscent or represents Thr-Gln-Thr-Pro, Pro-Leu-Thr-Gln-Thr-Pro, Leu-Thr-Gln-Thr-Pro or Pro; and Y is abscent or represents Val-Met), or a salt of the same. The method for improving the brain function comprises administering said peptide or a salt of the same.

Abstract: Provided is a method of treating a pathology associated with neural damage, the method comprising administering non-antigen specific polyclonal activated T cells and/or genetically modified T cells into the brain in a manner which prevents meningoencephalitis in the subject, thereby treating the pathology associated with neural damage. Also provided are devices for intrabrain and intrathecal administration of T cells, which comprise the brain-specific or non-antigen specific polyclonal activated T cells and/or genetically modified T cells and a catheter for intrabrain administration in a manner which prevents meningoencephalitis in a subject.

Abstract: The invention provides methods of screening a compound that can increase spine/excitatory synapse formation and/or numbers. The compound is identified by contacting Ephexin5 with a test compound and selecting the compounds that inhibit Rho GEF activity of Ephexin5. Additionally, the invention also provides methods for increasing spine/excitatory synapse formation and/or numbers by contacting a neuron with an Ephexin5 inhibitor.

Abstract: A method for preventing or treating a nervous disorder can include administrating to a person in need of such prevention or treatment a pharmaceutical preparation comprising, as an active ingredient, an ester of a decenoic acid. The ester of the decenoic acid can be selected from the group consisting of trans-2-decenoic acid ethyl ester, trans-2-decenoic acid methyl ester, trans-2-decenoic acid-2-decenyl ester, trans-2-decenoic acid cyclohexyl ester, trans-2-decenoic acid octyl ester, trans-2-decenoic acid isopropyl ester, trans-3-decenoic acid methyl ester, trans-3-decenoic acid ethyl ester, trans-9-decenoic acid methyl ester, and trans-9-decenoic acid ethyl ester.

Abstract: This invention relates to a recombinant human G-CSF (rhG-CSF) dimer and its use in the treatment of neurological disorder. In particular, upon ischemic neural injury in animal, this invention can be used to protect neurons with the use of rhG-CSF dimer such that function of injured nerves can be restored. Serum half-life of G-CSF dimer of this invention is prolonged and the biological activity thereof is increased.

Abstract: Indole-3-propionic acid as a marker and for treatment for Huntington Disease.

Abstract: The invention provides methods of treatment or prophylaxis of damaging effects of penetrative injury to the brain or other part of the central nervous system. The methods are based in part on results in a rodent model of penetrative ballistic injury showing that an inhibitor of PDF-95 NMDAR interaction is effective in inhibiting neurological deficits resulting from such injury. The methods are useful for treating subjects having or at risk of penetrative brain injury, including subjects who have been shot in the head or at risk of such injury (e.g., military or law enforcement personnel).

Abstract: Methods for treating a condition associated with proteoglycan production in a mammal are provided. The methods comprise the administration of at least one of a calmodulin antagonist, a transient receptor potential (TRP) channel inhibitor and a calmodulin-binding peptide to the mammal.

Abstract: Described herein is the identification of primate-specific glial cell line-derived neurotrophic factor opposite strand (GDNFOS) transcripts and encoded peptides. In particular embodiments, provided herein are three GDNFOS antisense transcripts, referred to as GDNFOS-1, GDNFOS-2 and GDNFOS-3. The GDNFOS-3 transcript encodes an ORF of 105 amino acids. Compositions comprising the GDNFOS transcripts and peptides are also provided by the present disclosure. Further provided are methods of treating a neurodegenerative or peripheral organ disease in a subject by administering a therapeutically effective amount of the disclosed GDNFOS nucleic acid molecules, peptides or compositions.

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

Abstract: The present invention relates to biomarkers and diagnostic methods for Alzheimer's disease and other neurodegenerative disorders. The invention also provides compositions for detecting the biomarker as well as compositions and methods useful for treating Alzheimer's disease and other neurodegenerative disorders.

Abstract: A method for treating a patient who has a neutralizing antibody to a type A1 botulinum toxin. The method includes administering 150 kDa type A neurotoxin from type A2 Clostridium botulinum (A2 NTX) to the patient. In accordance with the present invention, a problem can be solved of decrease in clinical response caused by a neutralizing antibody to a type A1 botulinum toxin produced when a patient is treated with a pharmaceutical preparation containing a type A1 botulinum toxin.

Abstract: A peptide compound of the following general formula (I) or (II): Ra—R1—R2—R3—R4—Rb??(I) or Ra—R4—R3—R2—R1—Rb??(II) wherein, R1 is a residue of amino acid H, R or K; R2 is a residue of amino acid A; R3 is a residue of amino acid E or D; R4 is a residue of amino acid E or D, Ra represents the N-terminal primary amine functions of the amino acid R1 or R4, either free or substituted with a protective group, Rb represents the hydroxyl function of the C-terminal carboxyl group of the amino acid R1 or R4, either free or substituted with a protective group.

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 AD-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.

Abstract: The invention relates to novel cyclodecapeptide compounds having formula (I) for use as drugs and, more specifically, for use in the diagnosis, prevention and/or treatment of neurodegenerative diseases, such as Wilson's disease and Alzheimer's disease, and for use in the diagnosis, prevention and/or treatment of poisoning with metal ions, such as copper and mercury ions. The invention also relates to pharmaceutical compositions comprising at least one compound having formula (I) as an active principle.

Abstract: A method of attenuating a biological effect of cocaine exposure in a primate. Such method includes administering to the primate an amount of a BChE-albumin fusion protein comprising the amino acid substitutions A227S, S315G, A356W, and Y360G, wherein the amount of the fusion protein is effective to cause attenuation of the biological effect of cocaine exposure in the primate.

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

Abstract: Disclosed are compositions and methods related to improving pharmacological properties of bioactive compounds targeting nervous system.

Abstract: A purified polypeptide, designated ULIP6, comprising the amino acid sequence SED ID No. 2 or an epitopic fragment of said polypeptide, comprising the sequence SEQ ID No. 4, is provided along with its nucleic acid sequences. In addition, antibodies to the polypeptide and methods of diagnosing paraneoplastic neurological syndromes and/or for the early diagnosis of the formation of cancerous tumors are also provided.

Abstract: The invention provides human signal peptide-containing proteins (HSPP) and polynucleotides which identify and encode HSPP. 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 expression of HSPP.

Abstract: An object of the present invention is to provide a medicament and method for treating lissencephaly patients. The present invention provides a lissencephaly therapeutic or preventive agent comprising a compound represented by the general formula (I): wherein R1 is lower alkyl substituted with lower alkoxy, lower alkyl substituted with a heterocyclic group, a heterocyclic group, or a group represented by the formula (IIa): wherein R4 is lower alkyl, R5 is lower alkylene, and m is an integer of 1 to 6; R2 is lower alkyl optionally substituted with phenyl; and R3 is lower alkyl optionally substituted with halogen, lower alkoxy, or phenyl; condensed polycyclic hydrocarbon; or hydrogen.

Abstract: The invention provides methods of treating or effecting prophylaxis of a patient having or at risk of developing symptoms of anxiety in which an effective regime of an agent that inhibits specific binding of PSD95 to an NMDA receptor is administered to a patient.