Abstract: The present invention is not to be limited in scope by the specific embodiments described herein. Indeed, various modifications of the invention in addition to those described herein will become apparent to those skilled in the art from the foregoing description and accompanying figures. Such modifications are intended to fall within the scope of the appended claims. Various publications are cited herein, the disclosures of which are incorporated by reference in their entireties.

Abstract: Methods of treating acute neuronal injury by utilizing a BACE polypeptide that binds to Nogo, or compositions comprising such BACE polypeptide.

Abstract: A method of identifying a modulator Nogo function, the method comprising: (i) providing (a) a BACE polypeptide; (b) a Nogo polypeptide; (c) a test agent under conditions that would permit binding of a BACE polypeptide (a) to a Nogo polypeptide (b) in the absence of the test agent (c) wherein said BACE polypeptide (a) is BACE or a variant thereof or a fragment of either thereof capable of binding Nogo; and polypeptide (b) is Nogo or a variant thereof or a fragment of either thereof capable of binding BACE; (ii) monitoring Nogo mediated activity; and (iii) determining thereby whether the test agent is a modulator of Nogo activity. Modulators identified by a method of the invention and use of such modulators in the manufacture of a medicament for the treatment of disorders responsive to the modulation of Nogo activity such as acute neuronal injury.

Abstract: The present invention is based on a novel direct interaction between a Presenilin and a novel protein identified herein and named Sambiasin-1, a homolog thereof named Sambiasin-2, as well as a protein complex further comprising a Nicastrin. Also comprised are uses of said components and complexes, as well as methods for use of the protein and the complex, inter alia, screening, diagnosis and therapy, as well as methods of preparing the complexes.

Abstract: A method of identifying a modulator of presenilin function, the method comprising: (i) providing (a) a polypeptide capable of binding a presenilin, which polypeptide comprises the amino acid sequence of SEQ ID NO: 1 or a functional variant thereof, or a fragment of either thereof which is capable of binding to presenilin; (b) a presenilin or a variant thereof or a fragment of either thereof capable of binding to a polypeptide which comprises the amino acid sequence of SEQ ID NO: 1; (c) a test substance under conditions that would permit binding of a polypeptide (a) to a presenilin (b) in the absence of the test substance; (ii) monitoring presenilin mediated activity; and (iii) determining thereby whether the test substance is a modulator of presenilin activity, a modulator identified by a method of the invention and use of a modulator identified by a method of the invention in the treatment of Alzheimer's disease.

Abstract: A method of identifying a modulator BACE function, the method comprising: (i) providing (a) a BACE polypeptide; (b) a Nogo polypeptide; (c) a test agentunder conditions that would permit binding of a BACE polypeptide (a) to a Nogo polypeptide (b) in the absence of the test agent (c) wherein said BACE polypeptide (a) is BACE or a variant thereof or a fragment of either thereof capable of binding Nogo; and polypeptide (b) is Nogo or a variant thereof or a fragment of either thereof capable of binding BACE; (i) monitoring BACE mediated activity; and (ii) determining thereby whether the test agent is a modulator of BACE activity. Modulators identified by a method of the invention and use of such modulators in the manufacture of a medicament for the treatment of disorders responsive to the modulation of BACE activity such as Alzheimer's disease.

Abstract: A method of identifying a modulator Nogo function, the method comprising:(i) providing (a) a BACE polypeptide; (b) a Nogo polypeptide; (c) a test agentunder conditions that would permit binding of a BACE polypeptide (a) to a Nogo polypeptide (b) in the absence of the test agent (c) wherein said BACE polypeptide (a) is BACE or a variant thereof or a fragment of either thereof capable of binding Nogo; and polypeptide (b) is Nogo or a variant thereof or a fragment of either thereof capable of binding BACE;(ii) monitoring Nogo mediated activity; and(iii) determining thereby whether the test agent is a modulator of Nogo activity. Modulators identified by a method of the invention and use of such modulators in the manufacture of a medicament for the treatment of disorders responsive to the modulation of Nogo activity such as acute neuronal injury.

Abstract: A method of identifying a modulator of presenilin function, the method comprising: (i) providing (a) a polypeptide capable of binding a presenilin, which polypeptide comprises the amino acid sequence of SEQ ID NO: 1 or a functional variant thereof, or a fragment of either thereof which is capable of binding to presenilin; (b) a presenilin or a variant thereof or a fragment of either thereof capable of binding to a polypeptide which comprises the amino acid sequence of SEQ ID NO: 1; (c) a test substance under conditions that would permit binding of a polypeptide (a) to a presenilin (b) in the absence of the test substance; (ii) monitoring presenilin mediated activity; and (iii) determining thereby whether the test substance is a modulator of presenilin activity, a modulator identified by a method of the invention and the use thereof in the treatment of Alzheimer's disease.