Medical Research Council

Duke University

Michel Goedert

Warren J Strittmatter

Philip Cohen

Allen D Roses

Donald E Schmechel

Karl H Weisgraber

Masato Hasegawa

Richard Anthony Crowther

Maria Grazia Spillantini

Ann M Saunders

Ross Jakes

Michael John Smith

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.

MAP kinases: polypeptides, polynucleotides and uses thereof

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.

Screening of agents for treatment of alzheimer's disease

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.

Methods and compositions for binding tau and MAP2c proteins

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Cambridge, United Kingdom

Michel Goedert