Abstract: a method of inhibiting a protein kinase that has a threonine or less bulky residue at the position equivalent to Thr 106 in SAPK2a/p38, and not mammalian SAPK2a/p38 or SAPK2b/p38?2, is provided, wherein the protein kinase is exposed to a pyridinyl imidazole inhibitor. The protein kinase may be a TGF? type-I or type-II receptor.

Abstract: The present inventions relates to substances which are capable of controlling the inclusion of exon (10) of the tau gene. The substances can reverse “wrong” tau splicing pattern and. Since “wrong” tau splicing patterns are associated with tauopathies that cause dementia, the substances can be used as therapeutic agents. The invention also provides a method for testing substances that control tau exon (10) inclusion. The method is suitable for a high throughput screening. Additional products which are useful for changing tau exon (10) expression or for performing the test method are described as well.

Abstract: The present invention relates to a method of identifying a compound which blocks the activation of a stress-activated protein kinase selected from the group consisting of SAPK4 and SAPK3 by SKK3. The method includes contacting the stress-activated protein kinase with the compound and determining whether the compound enhances or disrupts the interaction between the stress-activated protein kinase and SKK3. The invention further relates to a screening assay, a method of identifying agents able to influence the activity of a stress-activated protein kinase and a method of activating a stress-activated protein kinase.

Abstract: The present invention relates generally to methods and compositions for the diagnosis, modeling and treatment of tau-related pathologies. In particular, the present invention shows that mutations in the tau gene lead to neurofibrillary tangle formation. More specifically gene mutations are described that lead to alterations in ratios of tau isoforms are shown to lead to the formation of abnormal tau filaments.

Abstract: A method of screening an agent for potential use in the treatment of Alzheimer's disease, comprises reacting, in the presence of the agent, tau protein with a suitable sulphated carbohydrate under appropriate conditions to form filaments, and monitoring for the presence of filaments. Tau protein and sulphated carbohydrate, e.g. sulphated glycosaminoglycan, will react under appropriate conditions to form filaments, either paired helical filaments or straight filaments. If filament formation is affected when the reaction is carried out in the presence of an agent being screened, this is possibly due to an interfering, inhibiting or blocking effect of the agent. An agent which inhibits assembly of PHFs in vitro may also have an inhibiting effect in vivo and thus have potential therapeutic value in delaying the dementing effects of Alzheimer's disease. The invention can thus provide a screen to identify agents worthy of further investigation for use in the treatment of Alzheimer's disease.

Abstract: A method of combatting Alzheimer's disease which comprises increasing the binding of the tau protein in nerve cells of that subject, and/or the binding of MAP2c protein in nerve cells of that subject, to either Apolipoprotein E or an Apolipoprotein E fragments capable of binding tau and/or MAP2c. In one embodiment, the method comprises administering the ApoE or ApoE fragment to the subject; in another embodiment, the method comprises administering to the subject a vector capable of entering nerve cells, which vector then upregulates the expression of an ApoE or an ApoE fragment capable of binding tau and/or MAP2c in nerve cells. Compositions useful for carrying out these methods are also disclosed.