RU2012117230A - Способы модулирования аутофагии путем модулирования продуктов, усиливающих аутофагию генов - Google Patents
Способы модулирования аутофагии путем модулирования продуктов, усиливающих аутофагию генов Download PDFInfo
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Abstract
1. Способ ингибирования аутофагии в клетке, включающий приведение в контакт указанной клетки со средством, которое ингибирует активность продукта гена, выбранного из группы, состоящей из генов, приведенных в таблице 2.2. Способ по п.1, где ген выбран из группы, состоящей из генов, приведенных в таблице 4.3. Способ по п.1, где указанный ген выбран из группы, состоящей из генов, приведенных в таблице 6.4. Способ по п.1, где указанное средство представляет собой миРНК, кшРНК или антисмысловую молекулу РНК.5. Способ по п.3, где указанный ген представляет собой TPR или GPR18.6. Способ по п.5, где указанное средство представляет собой антитело, специфичное к продукту указанного гена.7. Способ по п.1, где указанный ген представляет собой RelA или NFκB.8. Способ по п.7, где указанный ген представляет собой RelA.9. Способ индукции аутофагии в клетке, включающий приведение в контакт указанной клетки со средством, которое усиливает активность продукта гена, выбранного из группы, состоящей из генов, приведенных в таблице 2 (наилучшие гены, которые снижают аутофагию).10. Способ по п.9, где указанный ген выбран из группы, состоящей из генов, приведенных в таблице 4.11. Способ по п.9, где указанный ген выбран из группы, состоящей из генов, приведенных в таблице 6.12. Способ по п.11, где указанный ген представляет собой TPR или GPR18.13. Способ по п.12, где указанное средство представляет собой антитело, специфичное к продукту указанного гена.14. Способ по п.9, где указанный ген представляет собой RelA или NFκB.15. Способ по п.14, где указанный ген представляет собой RelA.16. Способ лечения нейродегенеративного заболевания у индивидуума, включающий введение указанному индивидууму средства,
Claims (50)
1. Способ ингибирования аутофагии в клетке, включающий приведение в контакт указанной клетки со средством, которое ингибирует активность продукта гена, выбранного из группы, состоящей из генов, приведенных в таблице 2.
2. Способ по п.1, где ген выбран из группы, состоящей из генов, приведенных в таблице 4.
3. Способ по п.1, где указанный ген выбран из группы, состоящей из генов, приведенных в таблице 6.
4. Способ по п.1, где указанное средство представляет собой миРНК, кшРНК или антисмысловую молекулу РНК.
5. Способ по п.3, где указанный ген представляет собой TPR или GPR18.
6. Способ по п.5, где указанное средство представляет собой антитело, специфичное к продукту указанного гена.
7. Способ по п.1, где указанный ген представляет собой RelA или NFκB.
8. Способ по п.7, где указанный ген представляет собой RelA.
9. Способ индукции аутофагии в клетке, включающий приведение в контакт указанной клетки со средством, которое усиливает активность продукта гена, выбранного из группы, состоящей из генов, приведенных в таблице 2 (наилучшие гены, которые снижают аутофагию).
10. Способ по п.9, где указанный ген выбран из группы, состоящей из генов, приведенных в таблице 4.
11. Способ по п.9, где указанный ген выбран из группы, состоящей из генов, приведенных в таблице 6.
12. Способ по п.11, где указанный ген представляет собой TPR или GPR18.
13. Способ по п.12, где указанное средство представляет собой антитело, специфичное к продукту указанного гена.
14. Способ по п.9, где указанный ген представляет собой RelA или NFκB.
15. Способ по п.14, где указанный ген представляет собой RelA.
16. Способ лечения нейродегенеративного заболевания у индивидуума, включающий введение указанному индивидууму средства, которое усиливает активность продукта гена, выбранного из группы, состоящей из генов, приведенных в таблице 2.
17. Способ по п.16, где указанный ген выбран из группы, состоящей из генов, приведенных в таблице 4.
18. Способ по п.16, где указанный ген выбран из группы, состоящей из генов, приведенных в таблице 6.
19. Способ по п.18, где указанный ген представляет собой TPR или GPR18.
20. Способ по п.19, где указанное средство представляет собой антитело, специфичное к продукту указанного гена.
21. Способ по п.16, где указанный ген представляет собой RelA или NFκB.
22. Способ по п.21, где указанный ген представляет собой RelA.
23. Способ по п.16, где указанное нейродегенеративное заболевание выбрано из группы, состоящей из лейкодистрофии надпочечников, алкоголизма, болезни Александера, болезни Альперса, болезни Альцгеймера, бокового амиотрофического склероза, атаксии-телеангиэктазию, болезни Баттена, губкообразной энцефалопатии крупного рогатого скота, болезни Канавана, церебрального паралича, синдрома Кокейна, кортикобазальной дегенерации, болезни Крейтцфельда-Якоба, фатальной семейной бессонницы, лобно-височной лобарной дегенерации, болезни Гентингтона, ВИЧ-связанной деменции, болезни Кеннеди, болезни Краббе, деменции с тельцами Леви, нейроборрелиоза, болезни Мачадо-Джозефа, множественной системной атрофии, рассеянного склероза, нарколепсии, болезни Ниманна-Пика, болезни Паркинсона, болезни Пелицеуса-Мерцбахера, болезни Пика, первичного латерального склероза, прионных заболеваний, прогрессирующего надъядерного паралича, болезни Рефсума, болезни Сендхоффа, болезни Шильдера, подострой комбинированной дегенерации спинного мозга, вторичной для пернициозной анемии, болезни Шпильмейера-Фогта-Шегрена-Баттена, спинально-церебеллярной атаксии, спинальной мышечной атрофии, болезни Стила-Ричардсона-Ольшевского, сухотки спинного мозга и токсической энцефалопатии.
24. Способ по п.16, где указанное нейродегенеративное заболевание представляет собой протеинопатию.
25. Способ по п.24, где указанная протеинопатия выбрана из группы, состоящей из болезни Альцгеймера, болезни Паркинсона, деменции с тельцами Леви, ALS, болезни Гентингтона, спинально-церебеллярных атаксий и спинобульбарной мышечной атрофии.
26. Способ лечения заболевания у индивидуума, включающий введение указанному индивидууму средства, которое ингибирует активность продукта гена, выбранного из группы, состоящей из генов, приведенных в таблице 2 (наилучшие гены, которые снижают аутофагию), где указанное заболевание представляет собой злокачественную опухоль или панкреатит.
27. Способ по п.26, где ген выбран из группы, состоящей из генов, приведенных в таблице 4.
28. Способ по п.26, где указанный ген выбран из группы, состоящей из генов, приведенных в таблице 6.
29. Способ по п.26, где указанное средство представляет собой миРНК, кшРНК или антисмысловую молекулу РНК.
30. Способ по п.28, где указанный ген представляет собой TPR или GPR18.
31. Способ по п.30, где указанное средство представляет собой антитело, специфичное к продукту указанного гена.
32. Способ по п.26, где указанный ген представляет собой RelA или NFκB.
33. Способ по п.32, где указанный ген представляет собой RelA.
34. Способ по п.26, где указанное заболевание представляет собой злокачественную опухоль.
35. Способ по п.34, кроме того, включающий введение химиотерапевтического средства.
36. Способ по п.35, где химиотерапевтическое средство выбрано из группы, состоящей из: алтретамина, аспарагиназы, BCG, блеомицина сульфата, бусульфана, камптотецина, карбоплатина, кармустина, хлорамбуцила, цисплатина, кладрибина, 2-хлордезоксиаденозина, циклофосфамида, цитарабина, дакарбазина имидазола карбоксамида, дактиномицина, даунорубицина - дауномицина, дексаметазона, доксорубицина, этопозида, флоксуридина, фторурацила, флуоксиместерона, флутамида, флударабина, гозерелина, гидроксимочевины, идарубицина HCL, ифосфамида, интерферона α, интерферона α 2a, интерферона α 2b, интерферона α n3, иринотекана, лейковорина кальция, леупролида, левамизола, ломустина, магестрола, мелфалана, L-саркосилина, мелфалана гидрохлорида, MESNA, мехлорэтамина, метотрексата, митомицина, митоксантрона, меркаптопурина, паклитаксела, пликамицина, преднизона, прокарбазина, стрептозоцина, тамоксифена, 6-тиогуанина, тиотепы, топотекана, винбластина, винкристина и винорелбина тартрата.
37. Способ по п.34, кроме того, включающий проведение лучевой терапии.
38. Способ по п.26, где указанное заболевание представляет собой панкреатит.
39. Способ лечения протеинопатии у индивидуума, включающий введение указанному индивидууму средства, которое усиливает активность продукта гена, выбранного из группы, состоящей из генов, приведенных в таблице 2.
40. Способ по п.39, где указанный ген выбран из группы, состоящей из генов, приведенных в таблице 4.
41. Способ по п.39, где указанный ген выбран из группы, состоящей из генов, приведенных в таблице 6.
42. Способ по п.41, где указанный ген представляет собой TPR или GPR18.
43. Способ по п.42, где указанное средство представляет собой антитело, специфичное к продукту указанного гена.
44. Способ по п.39, где указанный ген представляет собой RelA или NFκB.
45. Способ по п.44, где указанный ген представляет собой RelA.
46. Способ по п.39, где указанная протеинопатия выбрана из группы, состоящей из дефицита α1-антитрипсина, спорадического миозита с тельцами включения, мышечной дистрофии плечевого пояса типа 2B и миопатии Миоши, болезни Альцгеймера, болезни Паркинсона, деменции с тельцами Леви, ALS, болезни Гентингтона, спинально-церебеллярных атаксий и спинобульбарной мышечной атрофии.
47. Способ определения того, является ли средство ингибитором аутофагии, причем способ включает стадию приведения в контакт клетки со средством, где клетка экспрессирует гетерологичный усиливающий аутофагию ген, где указанный усиливающий аутофагию ген выбран из группы, состоящей из генов, приведенных в таблице 2, причем снижение аутофагии в клетке указывает на то, что средство является ингибитором аутофагии.
48. Способ по п.47, где средство представляет собой низкомолекулярное соединение.
49. Способ по п.47, где средство представляет собой антитело.
50. Способ по п.47, где средство представляет собой ингибиторную молекулу РНК.
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- 2010-09-30 JP JP2012532326A patent/JP2013506687A/ja active Pending
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- 2010-09-30 CN CN2010800542999A patent/CN102639700A/zh active Pending
- 2010-09-30 US US13/499,314 patent/US20120301463A1/en not_active Abandoned
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- 2010-09-30 JP JP2012532325A patent/JP2013506686A/ja active Pending
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- 2010-09-30 KR KR1020127011288A patent/KR20120082906A/ko not_active Application Discontinuation
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- 2010-09-30 RU RU2012117230/10A patent/RU2012117230A/ru not_active Application Discontinuation
- 2010-09-30 CA CA2774999A patent/CA2774999A1/en not_active Abandoned
- 2010-09-30 WO PCT/US2010/050960 patent/WO2011041582A2/en active Application Filing
- 2010-09-30 AU AU2010300531A patent/AU2010300531A1/en not_active Abandoned
- 2010-09-30 BR BR112012007160A patent/BR112012007160A2/pt not_active IP Right Cessation
- 2010-09-30 CN CN2010800543027A patent/CN102869775A/zh active Pending
- 2010-09-30 MX MX2012003770A patent/MX2012003770A/es not_active Application Discontinuation
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WO2011041584A2 (en) | 2011-04-07 |
BR112012007160A2 (pt) | 2018-03-13 |
US20140004108A1 (en) | 2014-01-02 |
AU2016201939A1 (en) | 2016-04-21 |
CN102639700A (zh) | 2012-08-15 |
WO2011041584A3 (en) | 2011-05-26 |
CA2774998A1 (en) | 2011-04-07 |
JP2013506687A (ja) | 2013-02-28 |
JP2013506686A (ja) | 2013-02-28 |
EP2483407A2 (en) | 2012-08-08 |
JP2016040297A (ja) | 2016-03-24 |
CN102869775A (zh) | 2013-01-09 |
AU2010300531A1 (en) | 2012-05-24 |
US20160194631A1 (en) | 2016-07-07 |
KR20120082906A (ko) | 2012-07-24 |
US20120315244A1 (en) | 2012-12-13 |
CA2774999A1 (en) | 2011-04-07 |
US20120301463A1 (en) | 2012-11-29 |
BR112012007137A2 (pt) | 2015-09-15 |
MX2012003770A (es) | 2012-08-03 |
WO2011041582A3 (en) | 2011-09-29 |
WO2011041582A2 (en) | 2011-04-07 |
EP2483406A2 (en) | 2012-08-08 |
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