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1. WO2011056300 - PROCÉDÉS ET COMPOSITIONS POUR MODULER LES TAUX DE TAU

Note: Texte fondé sur des processus automatiques de reconnaissance optique de caractères. Seule la version PDF a une valeur juridique

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CLAIMS

What is claimed is:

1. A method for reducing the level of an acetylated Tau polypeptide in a cell, the method comprising contacting the cell with an agent that increases the activity of a polypeptide that deacetylates a Tau polypeptide in the cell and/or an agent that decreases the activity of a polypeptide that acetylates a Tau polypeptide in the cell.

2. The method of claim 1, wherein the method comprises contacting the cell with an agent that increases the activity of a polypeptide that deacetylates a Tau polypeptide in the cell and an agent that decreases the activity of a polypeptide that acetylates a Tau polypeptide in the cell.

3. The method of claim 1, wherein the cell is a neuron.

4. The method of claim 1, wherein the cell is a glial cell.

5. The method of claim 1, wherein the agent is not a sirtuin activator.

6. The method of claim 1, wherein the agent is a p300 inhibitor or a CBP inhibitor.

7. The method of claim 1, wherein the agent is an activator of SIRT1, SIRT2, or HDAC6.

8. The method of claim 1, wherein said contacting reduces the level of phosphorylated Tau polypeptide in the cell.

9. The method of claim 1, wherein said contacting increases the level of active Tau polypeptide in the cell.

10. A method for treating a tauopathy in an individual, the method comprising administering to the individual an effective amount of an agent that reduces the level of acetylated Tau in a neuron or a glial cell in the individual.

11. The method of claim 10, wherein the administering comprises administering to the individual an agent that increases the activity of a polypeptide that deacetylates a Tau polypeptide in a neuronal cell or a glial cell and an agent that decreases the activity of a polypeptide that acetylates a Tau polypeptide in a neuronal cell or a glial cell in combined effective amounts to treat the tauopathy.

12. The method of claim 10, wherein the tauopathy is frontotemporal dementia, Alzheimer's disease, progressive supranuclear palsy, corticobasal degeneration, Down syndrome, dementia pugilistica, inclusion-body myositis, or frontotemporal lobar degeneration.

13. The method of claim 10, wherein the agent that reduces the level of acetylated Tau is a p300/CBP inhibitor.

14. The method of claim 10, wherein the agent that reduces the level of acetylated Tau is a SIRT1 activator.

15. The method of claim 10, wherein said administering reduces the level of phosphorylated Tau in a neuron or glial cell in the individual.

16. The method of claim 10, wherein said administering increases the level of active Tau in a neuron or glial cell in the individual.

17. A method of diagnosing a cognitive impairment disorder in an individual, the method comprising detecting a level of acetylated Tau polypeptide in a biological sample obtained from the individual, wherein a level of acetylated Tau polypeptide that is higher than a normal control level indicates that the individual has a cognitive impairment disorder.

18. The method of claim 17, wherein the biological sample is cerebrospinal fluid, blood, plasma, or serum.

19. A method of identifying a candidate agent for treating a tauopathy, the method comprising:

a) contacting a sample comprising an acetyltransferase and a Tau polypeptide with a test agent; and

b) determining the effect of the test agent on the acetylation of the Tau polypeptide, wherein a test agent that reduces acetylation of the Tau polypeptide is a candidate agent for treating a tauopathy.

20. A method of identifying a candidate agent for treating a tauopathy, the method comprising:

a) contacting a sample comprising a deacetylase and a Tau polypeptide with a test agent; and b) determining the effect of the test agent on the acetylation of the Tau polypeptide, wherein a test agent that increases deacetylation of the Tau polypeptide is a candidate agent for treating a tauopathy.