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• • C—CHEMISTRY; METALLURGY
  • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
  • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
  • C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
  • C12N9/10—Transferases (2.)
  • C12N9/12—Transferases (2.) transferring phosphorus containing groups, e.g. kinases (2.7)
  • C12N9/1205—Phosphotransferases with an alcohol group as acceptor (2.7.1), e.g. protein kinases
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P25/00—Drugs for disorders of the nervous system
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P25/00—Drugs for disorders of the nervous system
  • A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P25/00—Drugs for disorders of the nervous system
  • A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
  • A61P25/16—Anti-Parkinson drugs
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P25/00—Drugs for disorders of the nervous system
  • A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
  • A61P7/10—Antioedematous agents; Diuretics
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P9/00—Drugs for disorders of the cardiovascular system
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K38/00—Medicinal preparations containing peptides

Definitions

• JNK3 The tissue distribution of isoforms is widely dispersed with varying levels of expression.
• JNK3 isoforms are more selectively expressed in the brain (for example in the hippocampus or in the cerebellum (Mohit et al. 1995)), but also in the heart and the testes.
• a growing number of results underlines the importance of JNK3 in the phenomena of neurodegeneration and neuronal death by apoptosis, however, the mode of action of JNK3 is not known to date.
• JNK3 immunoreactivity is diffuse and only cytoplasmic (Zhang et al. 1998).
• JNK3 immunoreactivity is diffuse and only cytoplasmic (Zhang et al. 1998).
• the deletion of the JNK3 gene in mice allows resistance to kainic acid, a glutamate receptor agonist participating in the phenomena of excitotoxicity.
• the authors describe in detail the reduction of epileptic effects and the prevention of neuronal death by apoptosis in the hippocampus, after injection of kainic acid in these mice deleted for JNK3.
• a mutated form of PBS2 is expressed in the strain indicated above: PBS2 DD (Wurgler-Mu ⁇ hy et al. 1997) which has a toxic effect on the growth of yeast.
• PBS2 DD Wood-Mu ⁇ hy et al.
• This toxicity depends on the activity of the downstream protein kinase, which according to the present invention is a new isoform of JNK3.
• Inhibitors of these new isoform of JNK3 are likely in this case to inhibit the toxic effect of mutated PBS2 and thus allow the restoration of the growth of this strain.
• Another subject of the invention relates to compounds or ligands capable of inhibiting the activity of the polypeptides according to the invention and capable of being obtained using one of these microorganisms as a screening tool
• Another subject of the invention relates to the use of a compound or ligand identified and / or obtained according to one of the methods described above as a medicament.
• Such compounds are in fact capable of being used for the prevention, improvement or treatment of various pathologies caused by neuronal degeneration, among which may be mentioned Alzheimer's disease, Huntington's disease and Parkinson's disease , senile dementia and those due to AIDS, head trauma, anoxia, hypoxia and cerebral edema.
• the identification of the specific partner polypeptides of the different isoforms of JNK3 can be carried out by the technique of cloning in double hybrid according to the techniques described by Fields et al. 1994; the bait protein can in particular be the whole protein JNK3 ⁇ N ⁇ l or JNK3 ⁇ N ⁇ 2, or the N-terminal extension of 38 amino acids of JNK3 which is absent in the JNK3 ⁇ N isoforms.
• the bait protein can in particular be the whole protein JNK3 ⁇ N ⁇ l or JNK3 ⁇ N ⁇ 2, or the N-terminal extension of 38 amino acids of JNK3 which is absent in the JNK3 ⁇ N isoforms.

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• Micro-Organisms Or Cultivation Processes Thereof (AREA)
• Peptides Or Proteins (AREA)
• Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
• Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
• Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
• Enzymes And Modification Thereof (AREA)

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• 2000
  • 2000-01-19 EP EP00900608A patent/EP1144651A1/fr not_active Withdrawn
  • 2000-01-19 NZ NZ512986A patent/NZ512986A/xx not_active Application Discontinuation
  • 2000-01-19 IL IL14395000A patent/IL143950A0/xx unknown
  • 2000-01-19 JP JP2000594932A patent/JP2002534982A/ja not_active Withdrawn
  • 2000-01-19 AU AU30560/00A patent/AU3056000A/en not_active Abandoned
  • 2000-01-19 WO PCT/FR2000/000104 patent/WO2000043524A1/fr not_active Application Discontinuation
  • 2000-01-19 CA CA002358914A patent/CA2358914A1/fr not_active Abandoned
• 2001
  • 2001-07-19 NO NO20013568A patent/NO20013568L/no not_active Application Discontinuation
  • 2001-07-19 US US09/909,650 patent/US6649388B2/en not_active Expired - Lifetime

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