Abstract: The present invention relates to the field of disorders of the central nervous system, in particular neurological and psychiatric disorders, and the prevention and/or treatment thereof. In particular, the present invention relates to the finding that soluble amyloid precursor protein a (sAPP?) presents a particular binding site, which allows for binding to the GABABR1a receptor, thereby causing an agonistic effect through specific binding to Sushi domain 1 of GABABR1a. As a result, the frequencies of excitatory and inhibitory postsynaptic currents are reduced. Accordingly, the invention provides compounds able to interfere with the association of sAPP? with Sushi domain 1 of GABABR1a and as such with selective impairment of GABABR1sa beneficial in neurological and psychiatric disorders. The invention as well provides methods and (high content) screening assays for the production of said compounds.

Abstract: The present invention relates to the field of disorders of the central nervous system, in particular neurological and psychiatric disorders, and the prevention and/or treatment thereof. In particular, the present invention relates to the finding that soluble amyloid precursor protein ? (sAPP?) presents a particular binding site, which allows for binding to the GABABR1a receptor, thereby causing an agonistic effect through specific binding to Sushi domain 1 of GABABR1a. As a result, the frequencies of excitatory and inhibitory postsynaptic currents are reduced. Accordingly, the invention provides compounds able to interfere with the association of sAPP? with Sushi domain 1 of GABABR1a and as such with selective impairment of GABABR1a beneficial in neurological and psychiatric disorders. The invention as well provides methods and (high content) screening assays for the production of said compounds.