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1. WO2006054979 - ABNORMALITIES OF PHOSPHATASE 2A (PP2A) FOR DIAGNOSIS AND TREATMENT OF ALZHEIMER’S DISEASE

Publication Number WO/2006/054979
Publication Date 26.05.2006
International Application No. PCT/US2004/038160
International Filing Date 15.11.2004
IPC
C12Q 1/68 2006.1
CCHEMISTRY; METALLURGY
12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
QMEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
1Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
68involving nucleic acids
C07H 21/04 2006.1
CCHEMISTRY; METALLURGY
07ORGANIC CHEMISTRY
HSUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
21Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
04with deoxyribosyl as saccharide radical
CPC
C12Q 1/6883
CCHEMISTRY; METALLURGY
12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
QMEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS
1Measuring or testing processes involving enzymes, nucleic acids or microorganisms
68involving nucleic acids
6876Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
6883for diseases caused by alterations of genetic material
C12Q 2600/136
CCHEMISTRY; METALLURGY
12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
QMEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS
2600Oligonucleotides characterized by their use
136Screening for pharmacological compounds
C12Q 2600/158
CCHEMISTRY; METALLURGY
12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
QMEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS
2600Oligonucleotides characterized by their use
158Expression markers
G01N 33/6896
GPHYSICS
01MEASURING; TESTING
NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
33Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
48Biological material, e.g. blood, urine
50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
68involving proteins, peptides or amino acids
6893related to diseases not provided for elsewhere
6896Neurological disorders, e.g. Alzheimer's disease
Applicants
  • BLANCHETTE ROCKEFELLER NEUROSCIENCES INSTITUTE [US]/[US] (AllExceptUS)
  • ZHAO, Wei-Qin [AU]/[US] (UsOnly)
  • ALKON, Daniel, L. [US]/[US] (UsOnly)
Inventors
  • ZHAO, Wei-Qin
  • ALKON, Daniel, L.
Agents
  • LONGTON, Enrique, D.
Priority Data
Publication Language English (en)
Filing Language English (EN)
Designated States
Title
(EN) ABNORMALITIES OF PHOSPHATASE 2A (PP2A) FOR DIAGNOSIS AND TREATMENT OF ALZHEIMER’S DISEASE
(FR) ANOMALIES DE LA PHOSPHATASE 2A (PP2A) POUR LE DIAGNOSTIC ET LE TRAITEMENT DE LA MALADIE D'ALZHEIMER
Abstract
(EN) This invention relates to methods of diagnosing Alzheimer's disease and methods of screening for compounds for the treatment or prevention of Alzheimer's disease. The methods are based upon newly discovered differences in protein phosphatase 2A (PP2A) function and related molecular events in Alzheimer's disease cells compared to control cells. In one embodiment, differences in basal PP2A gene expression in Alzheimer's cells are compared to controls. In another embodiment differences in PP2A protein and enzyme activity are compared in test and control cells. In another embodiment differences in response to substances that inhibit PP2A function are compared. Still another embodiment detects differences in the subcellular distribution of phosphorylated Erkl/2, a substrate of PP2A, in normal and Alzheimer's disease cells. The detection of Alzheimer's disease-specific differences in PP2A function and related events in peripheral tissues provides the basis for highly practical and efficient tests and diagnostic test kits for the early diagnosis of Alzheimer's disease, as well as providing a biochemical basis for identifying therapeutic targets for drug development.
(FR) Cette invention concerne des procédés de diagnostic de la maladie d'Alzheimer et des procédés de recherche par criblage de composés pour le traitement ou la prévention de la maladie d'Alzheimer. Les procédés sont basés sur des différences nouvellement découvertes dans le fonctionnement de la protéine phosphatase 2A (PP2A) et des événements moléculaires apparentés dans les cellules de la maladie d'Alzheimer par rapport à des cellules témoins de référence. Dans un mode de réalisation, on détecte par comparaison les différences dans l'expression du gène de la PP2A basale entre les cellules d'Alzheimer et des témoins de référence. Dans un autre mode de réalisation, on détecte par comparaison les différences dans l'activité de la protéine PP2A et de l'enzyme entre des cellules testées et des cellules témoins de référence. Dans un autre mode de réalisation on détecte par comparaison les différences dans la réponse à des substances qui inhibent le fonctionnement de la PP2A. Encore un autre mode de réalisation détecte les différences dans la distribution subcellulaire d'Erkl/2 phosphorylé, un substrat de la PP2A, entre des cellules normales et des cellules de la maladie d'Alzheimer. La détection de différences spécifiques à la maladie d'Alzheimer dans le fonctionnement de la PP2A et des événements apparentés dans des tissus périphériques procure la base pour des tests extrêmement pratiques et efficaces et des kits de test de diagnostic pour le diagnostic précoce de la maladie d'Alzheimer, ainsi qu'elle procure une base biochimique pour identifier des cibles thérapeutiques pour le développement de médicaments.
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