Abstract: The present invention relates to the field of neurological disorders and more particularly to the field of Alzheimer's disease. Specifically, the invention provides extracellular targets for Alzheimer's disease selected from the tetraspanin web family and associated proteins. In addition, methods are provided for the use of siRNAs and antibodies against the targets for inhibition of amyloid-beta production and, hence, for the treatment of Alzheimer's disease.

Abstract: The invention relates to the identification of microRNAs whose expression is diminished in neurodegenerative disorders. In particular, the identified microRNAs can be used for the downregulation of the beta-secretase (BACE1) in mammalian brain and hence for the treatment of Alzheimer's disease.

Abstract: The present invention relates to the field of amyloid disorders, more particularly to the field of diseases where protein misfolding leads to the generation of insoluble amyloid fibers in tissues and organs. The invention provides methods for the production of soluble, toxic amyloid oligomers. The invention further provides assays using the amyloid oligomers to screen for molecules that interfere with the toxicity of the oligomers.

Abstract: The current invention relates to the field of neurodevelopmental disorders and more particularly to the field of neuropsychiatric disorders. The invention provides non-human, transgenic animal models for said neurodevelopmental disorders such as schizophrenia, bipolar disorders, compulsive disorders and the like. The animals also have applications in the field of Alzheimer's Disease and other disorders in which ?-secretase activity has a role.

Abstract: The present invention relates to the identification of the molecular binding domains between presenilins and its substrates such as amyloid precursor protein and telencephalin. These binding domains can be efficiently used in drug screening assays to screen for compounds capable of modulating the interaction between presenilins and type I transmembrane proteins. The invention further relates to compounds capable of modulating the interaction.

Abstract: The present invention relates to the identification of the molecular binding domains between presenilins and its substrates such as amyloid precursor protein and telencephalin. These binding domains can be efficiently used in drug screening assays to screen for compounds capable of modulating the interaction between presenilins and type I transmembrane proteins. The invention further relates to compounds capable of modulating the interaction.

Abstract: The invention involves a method of stereotactic and viral vector-mediated gene transfer to produce animals harboring in their neural tissue a polynucleotide sequence, an allelic variant, minigene or a homolog thereof, that encodes for &agr;-synuclein or functional homnologues thereof and overexpresses ccsynuclein or functional homologues thereof locoregional in said neural tissue. Overexpression of &agr;-synuclein is associated with locoregional pathology in the neural tissue as evidenced by histology and neurodegeneration as evidenced by histology. These animals can be used in pharmaceutical screening and for in vivo modelling of &agr;-synuclein biochemistry.

Abstract: The present invention relates to the field of neurological and physiological dysfunctions associated with Alzheimer's disease, more particularly to mutant embryonic stem (ES) cell lines characterized by no detectable &ggr;-secretase activity, derived from double presenilin (PS 1 and PS 2) knockout mice embryos. These cell lines can be used for in vitro screening of molecules and products involved in regulated intramembrane proteolysis of proteins such as the PP, the APP-like proteins, Notch, Ire-1p, and other integral membrane proteins to identify proteases responsible for the latter proteolysis, like gamma-secretases, or proteins involved in the control of these proteolytic activities. These mutant ES cell lines can be manipulated to differentiate into fibroblasts, neurons, or myocytes or can be used to generate novel transgenic mice. Moreover, a reporter system comprising a chimeric molecule to detect the above-mentioned intramembrane proteolysis or modulators thereof has been developed.