Abstract: Methods and means for the identification of meprin-? and meprin-? as novel ?-secretases and antagonists thereof for use in the treatment of amyloidosis.

Abstract: The invention relates to novel pyrrolidine derivatives of formula (I): wherein R1, R2 and R3 are as defined herein, as inhibitors of glutaminyl cyclase (QC, EC 2.3.2.5). QC catalyzes the intramolecular cyclization of N-terminal glutamine residues into pyroglutamic acid (5-oxo-prolyl, pGlu*) under liberation of ammonia and the intramolecular cyclization of N-terminal glutamate residues into pyroglutamic acid under liberation of water.

Abstract: A novel method for detection of A? peptides, in particular in plasma, and to the use of A? peptides for diagnosis of Alzheimer's disease.

Abstract: The present invention relates to novel inhibitors of glutaminyl cyclase and combinations thereof for the treatment of neuronal disorders, especially Alzheimer's disease, Down Syndrome, Parkinson disease, Chorea Huntington, pathogenic psychotic conditions, schizophrenia, impaired food intake, sleep-wakefulness, impaired homeostatic regulation of energy metabolism, impaired autonomic function, impaired hormonal balance, impaired regulation, body fluids, hypertension, fever, sleep dysregulation, anorexia, anxiety related disorders including depression, seizures including epilepsy, drug withdrawal and alcoholism, neurodegenerative disorders including cognitive dysfunction and dementia.

Abstract: A knock-out non-human animal, in particular a mouse, carrying a QPCTL knock-out mutation. Additionally, respective cells and cell lines and methods and compositions for evaluating agents that affect QPCTL, for use in compositions for the treatment of QPCTL-related diseases are disclosed.

Abstract: The invention provides compounds of general formula (I) or a pharmaceutically acceptable salt, polymorph or solvate thereof, including all tautomers and stereoisomers thereof, wherein K, W, X; Y and Z are described throughout the description and claims. The compounds of the present invention are useful as inhibitors of prolyl endopeptidase (PEP, EC 3.4.21.26) and/or IL-6.

Abstract: Compounds of formula (I), combinations and uses thereof for disease therapy, or a pharmaceutically acceptable salt or solvate thereof, including all tautomers, stereoisomers and polymorphs thereof wherein: R1 represents C2-8alkyl; C2-8alkenyl; —(C1-6alkyl)-aryl; —(C1-6alkyl)-heteroaryl; —(C1-6alkyl)-carbocyclyl; —(C1-6alkyl)-heterocyclyl; -aryl; -heteroaryl; -carbocyclyl or -heterocyclyl; wherein said aryl or heteroaryl groups may be optionally substituted by one or more substituents selected from, C1-4alkyl, C1-4-fluoroalkyl, C1-4alkoxy, C1-4-fluoroalkoxy, hydroxy, —SO2(C1-4alkyl), —SO2N(C1-4alkyl)(C1-4alkyl), —SOC1-4alkyl, —SOC3-6cycloalkyl —C(O)O(C1-4alkyl), benzyloxy and phenyl; and wherein said carbocyclyl and heterocyclyl groups may be optionally substituted by one or more substituents selected from —C1-4 alkyl, —C1-4 alkoxy, hydroxyl, halogen and oxo; R2 represents H; C1-4alkyl or halogen; R3 represents H; C1-4alkyl or halogen; and R4 represents H; C1-4alkyl or halogen.

Abstract: There is disclosed herein methods for using compounds of formula (I), wherein: R1, R2, R3, R4 and R5 are defined throughout the description and the claims. The compounds of formula (I) are useful for the treatment of neurological diseases and neurodegenerative diseases, e.g. anxiety, depression, Alzheimer's disease etc.

Abstract: The present invention provides a method for the treatment of neuronal disorders, in a mammal such as a human, which method comprises administering an effective, non-toxic and pharmaceutically acceptable amount of at least one QC-inhibitor, optionally in combination with at least one agent, selected from the group consisting of PEP-inhibitors, LiCl, inhibitors of DP IV/DP IV-like enzymes, NPY-receptor ligands, NPY agonists, NPY antagonists, ACE-inhibitors, PIMT enhancers, inhibitors of beta secretases, inhibitors of gamma secretases and inhibitors of neutral endopeptidase, to a mammal in need thereof.

Abstract: The present invention relates to compounds of formula (I), combinations and uses thereof for disease therapy, wherein: R1 represents heteroaryl, -carbocyclyl-heteroaryl, -alkenylheteroaryl or -alkylheteroaryl; R2 represents alkyl, which may optionally be substituted by one or more groups selected from amino, halogen, hydroxyl, -alkoxy, -thioalkyl, —C(O)O-alkyl and —C(O)OH; carbocyclyl, which may optionally be substituted by one or more groups selected from alkyl, haloalkyl, amino, halogen, hydroxyl, alkoxy-, -thioalkyl, —C(O)O-alkyl and —C(O)OH; alkenyl; alkynyl; -alkyl-aryl; -alkyl-heteroaryl; -alkyl-heterocyclyl; -alkyl-carbocyclyl; -aryl-heteroaryl; -heteroaryl-aryl; -heteroaryl-heteroaryl; -aryl-aryl; -aryl (monocyclic or bicyclic); heteroaryl (monocyclic or bicyclic); heterocyclyl; or R2 together with R4 may form a carbocyclyl group optionally substituted by one or more alkyl groups; R3 represents alkyl, which may optionally be substituted by one or more groups selected from amino, halogen, hydroxyl

Abstract: The present invention provides novel physiological substrates of mammalian glutaminyl cyclase (QC, EC 2.3.2.5), new effectors of QC, methods for screening for such effectors, and the use of such effectors and pharmaceutical compositions comprising such effectors for the treatment of conditions that can be treated by modulation of QC-activity. Preferred compositions additionally comprise inhibitors of DP IV or DP IV-like enzymes for the treatment or alleviation of conditions that can be treated by modulation of QC- and DP IV-activity.

Abstract: There is disclosed herein compounds of formula (I), wherein: R1, R2, R3, R4 and R5 are defined throughout the description and the claims. The compounds of formula (I) are useful for the treatment of neurological diseases and neurodegenerative diseases, e.g. anxiety, depression, Alzheimer's disease etc.

Abstract: The present invention relates in general to an inhibitor of a glutaminyl peptide cyclotransferase-like protein (QPCTL), and the use thereof for the treatment and/or prevention of an inflammatory disease or disorder selected from the group consisting of (a) chronic and acute inflammations, e.g. rheumatoid arthritis, atherosclerosis, restenosis, pancreatitis; (b) other inflammatory diseases, e.g. neuropathic pain, graft rejection/graft failure/graft vasculopathy, HIV infections/AIDS, gestosis, tuberous sclerosis, Guillain-Barré syndrome, chronic inflammatory demyelinising polyradiculoneuropathy and multiple sclerosis; (c) neuroinflammation; and (d) neurodegenerative diseases, e.g. mild cognitive impairment (MCI), Alzheimer's disease, neurodegeneration in Down Syndrome, Familial British Dementia, and Familial Danish Dementia, which may result from neuroinflammation.

Abstract: Compounds of general formula (I): wherein R1, R2, R3, R4, X and Y are as defined herein are inhibitors of glutaminyl cyclase and are therefore useful in treating conditions that can be treated by modulation of glutaminyl cyclase activity.

Abstract: Monoclonal antibodies which bind specifically to the proinflammatory cytokine pyroglutamate MCP-1 (MCP-1 N1pE) are described.

Abstract: Inhibitors of prolyl endopeptidase of formula 1 W—KCONH—X—CON—Y—CO—Z??(1) wherein K, W, X, Y and Z are specified in the description. The compounds are useful for the treatment of diseases such as mild cognitive impairment (MCI), Alzheimer's disease, Down Syndrome, Parkinson disease and Chorea Huntington.

Abstract: The present invention relates to novel inhibitors of prolyl endopeptidase of formula 1 W—KCONH—X—CON—Y—CO—Z??(1) wherein K, W, X, Y and Z are specified in the description. The compounds are useful for the treatment of diseases such as mild cognitive impairment (MCI), Alzheimer's disease, Down Syndrome, Parkinson disease and Chorea Huntington.

Abstract: Physiological substrates of mammalian glutaminyl cyclase (QC, EC 2.3.2.5), new effectors of QC, methods for screening for such effectors, and the use of such effectors and pharmaceutical compositions comprising such effectors for the treatment of conditions that can be treated by modulation of QC-activity. Preferred compositions additionally comprise inhibitors of DP IV or DP IV-like enzymes for the treatment or alleviation of conditions that can be treated by modulation of QC- and DP IV-activity.

Abstract: A method for predicting, diagnosing and prognosticating a neurodegenerative disease, such as Alzheimer's disease (AD), Mild Cognitive Impairment (MCI) and neurodegeneration in Down's syndrome (NDS) using glutaminyl cyclase (QC) as a diagnostic/prognostic indicator. The use of antibodies binding to QC and kits for performing said diagnostic method are also provided.

Abstract: Compounds that act as inhibitors of QC including those represented by the general formulae 1 to 9: and combinations thereof for the treatment of neuronal disorders, especially Alzheimer's disease, Down Syndrome, Parkinson disease, Corea Huntington, pathogenic psychotic conditions, schizophrenia, impaired food intake, sleep-wakefulness, impaired homeostatic regulation of energy metabolism, impaired autonomic function, impaired hormonal balance, impaired regulation, body fluids, hypertension, fever, sleep dysregulation, anorexia, anxiety related disorders including depression, seizures including epilepsy, drug withdrawal and alcoholism, neurodegenerative disorders including cognitive dysfunction and dementia.