UY25604A1 - METHOD FOR THE IDENTIFICATION OF PRESENYLINASE INHIBITORS - Google Patents
METHOD FOR THE IDENTIFICATION OF PRESENYLINASE INHIBITORSInfo
- Publication number
- UY25604A1 UY25604A1 UY25604A UY25604A UY25604A1 UY 25604 A1 UY25604 A1 UY 25604A1 UY 25604 A UY25604 A UY 25604A UY 25604 A UY25604 A UY 25604A UY 25604 A1 UY25604 A1 UY 25604A1
- Authority
- UY
- Uruguay
- Prior art keywords
- presenilin
- fusion protein
- amount
- measured
- cell
- Prior art date
Links
Classifications
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/573—Immunoassay; Biospecific binding assay; Materials therefor for enzymes or isoenzymes
-
- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
- G01N33/6893—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids related to diseases not provided for elsewhere
- G01N33/6896—Neurological disorders, e.g. Alzheimer's disease
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Chemical & Material Sciences (AREA)
- Immunology (AREA)
- Medicinal Chemistry (AREA)
- Molecular Biology (AREA)
- Urology & Nephrology (AREA)
- Hematology (AREA)
- General Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Physics & Mathematics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Pathology (AREA)
- Biotechnology (AREA)
- Cell Biology (AREA)
- Pharmacology & Pharmacy (AREA)
- Organic Chemistry (AREA)
- Microbiology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Food Science & Technology (AREA)
- Veterinary Medicine (AREA)
- Analytical Chemistry (AREA)
- Biochemistry (AREA)
- General Physics & Mathematics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Hospice & Palliative Care (AREA)
- Psychiatry (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Peptides Or Proteins (AREA)
- Investigating Or Analysing Biological Materials (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
La presente invención proporciona métodos para la identificación de inhibidores de la presenilinasa, sustancias identificables con dichos métodos, su uso en la elaboración de un medicamento para el tratamiento de enfermedades neurodegenerativas, preferentemente la enfermedad de Alzheimer, y composiciones farmacéuticas que los contienen. El método para identificar una sustancia capaz de reducir o eliminar la actividad de la presenilinasa se caracteriza por las siguientes etapas: a) se cultiva una célula o línea celular que expresa dicha actividad de presenilinasa y una proteína de fusión, comprendiendo dicha proteína de fusión la presenilina 1 o presenilina 2 de longitud completa y un reportero, b) dicha célula o línea celular se incuba con un compuesto de ensayo, c) empleando el reportero, se mide la cantidad de proteína de fusión de longitud completa, d) la cantidad de proteína de fusión de longitud completa medida se compara con la cantidad de proteína de fusión de longitud completa medida para un testigo. La etapa c) se caracteriza además por las etapas: a) se inmovilizan sobre una superficie sólida anticuerpos específicos para la porción C-terminal de la presenilina 1 o la presenilina 2, b) se extrae la proteína de dicha célula o línea celular después del cultivo, c) dichos extractos de proteína se incuban con dichos anticuerpos, d) se mide la cantidad de proteína de fusión de longitud completa unida por dichos anticuerpos, mediante la detección del reportero. Estos métodos reducen o eliminan: la segmentación autoproteolítica de la presenilina, la actividad de la gamma-secretasa. Método en el que la sustancia previene la segmentación de la presenilina 1 en fragmentos de segmentación endoproteolítica regulada que son el fragmento N-terminal (NTF) y el fragmento C-terminal (CTF).The present invention provides methods for the identification of presenilinase inhibitors, substances identifiable by such methods, their use in the manufacture of a medicament for the treatment of neurodegenerative diseases, preferably Alzheimer's disease, and pharmaceutical compositions containing them. The method for identifying a substance capable of reducing or eliminating presenilinase activity is characterized by the following steps: a) a cell or cell line that expresses said presenilinase activity and a fusion protein is cultured, said fusion protein comprising: full length presenilin 1 or presenilin 2 and a reporter, b) said cell or cell line is incubated with a test compound, c) using the reporter, the amount of full length fusion protein is measured, d) the amount of Measured full length fusion protein is compared to the amount of measured full length fusion protein for a control. Step c) is further characterized by steps: a) antibodies specific for the C-terminal portion of presenilin 1 or presenilin 2 are immobilized on a solid surface, b) the protein is extracted from said cell or cell line after culture, c) said protein extracts are incubated with said antibodies, d) the amount of full-length fusion protein bound by said antibodies is measured by reporter detection. These methods reduce or eliminate: the autoproteolytic cleavage of presenilin, the activity of gamma-secretase. Method in which the substance prevents the segmentation of presenilin 1 into fragments of regulated endoproteolytic segmentation that are the N-terminal fragment (NTF) and the C-terminal fragment (CTF).
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP98112688 | 1998-07-09 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| UY25604A1 true UY25604A1 (en) | 2000-02-23 |
Family
ID=8232244
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| UY25604A UY25604A1 (en) | 1998-07-09 | 1999-07-09 | METHOD FOR THE IDENTIFICATION OF PRESENYLINASE INHIBITORS |
Country Status (7)
| Country | Link |
|---|---|
| EP (1) | EP1095279A1 (en) |
| JP (1) | JP2002520031A (en) |
| AR (1) | AR020107A1 (en) |
| AU (1) | AU5034099A (en) |
| CA (1) | CA2332344A1 (en) |
| UY (1) | UY25604A1 (en) |
| WO (1) | WO2000003248A1 (en) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE10000161A1 (en) * | 2000-01-06 | 2001-07-19 | Boehringer Ingelheim Pharma | Determining test substances that inhibit protease, involves incubating cells expressing fusion protein having substrate with cleavage site for protease and reporter, measuring cleaved reporter and comparing with standard |
| WO2001075435A2 (en) * | 2000-04-03 | 2001-10-11 | Bristol-Myers Squibb Company | Fluorescence assay for gamma-secretase activity and inhibitors |
| JP2021525245A (en) * | 2018-05-22 | 2021-09-24 | ザ ブリガム アンド ウィメンズ ホスピタル インコーポレイテッドＴｈｅ Ｂｒｉｇｈａｍ ａｎｄ Ｗｏｍｅｎ’ｓ Ｈｏｓｐｉｔａｌ， Ｉｎｃ． | Gene therapy for Alzheimer's disease |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1997027296A1 (en) * | 1996-01-26 | 1997-07-31 | Hsc Research And Development Limited Partnership | Nucleic acids and proteins related to alzheimer's disease, and uses therefor |
| GB9608657D0 (en) * | 1996-04-26 | 1996-07-03 | Smithkline Beecham Plc | Novel treatment |
| JP2002505664A (en) * | 1997-04-24 | 2002-02-19 | ザ ジェネラル ホスピタル コーポレイション | Method for screening for a purified 20 kDa C-terminal fragment of presenilin 2 and a compound that inhibits the proteolysis of presenilin 2 |
-
1999
- 1999-07-07 AR ARP990103295A patent/AR020107A1/en active Pending
- 1999-07-08 WO PCT/EP1999/004805 patent/WO2000003248A1/en not_active Application Discontinuation
- 1999-07-08 EP EP99934634A patent/EP1095279A1/en not_active Withdrawn
- 1999-07-08 AU AU50340/99A patent/AU5034099A/en not_active Abandoned
- 1999-07-08 JP JP2000559432A patent/JP2002520031A/en active Pending
- 1999-07-08 CA CA002332344A patent/CA2332344A1/en not_active Abandoned
- 1999-07-09 UY UY25604A patent/UY25604A1/en not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| JP2002520031A (en) | 2002-07-09 |
| WO2000003248A1 (en) | 2000-01-20 |
| AU5034099A (en) | 2000-02-01 |
| CA2332344A1 (en) | 2000-01-20 |
| AR020107A1 (en) | 2002-04-10 |
| EP1095279A1 (en) | 2001-05-02 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| 109 | Application deemed to be withdrawn |
Effective date: 20110324 |