Human pluripotent stem cells are differentiated in vitro into forebrain subdomain structures, which are then fused to generate an integrated system for use in analysis, screening programs, and the like.

Provided is a screening method for an agent for treating or preventing tauopathy, the method comprising (1) a step of contacting an NMDA-type glutamate receptor with a tau oligomer in the presence or absence of a candidate compound, and (2) a step of evaluating a direct binding of the tau oligomer to the NMDA-type glutamate receptor. Further provided is a test method for tauopathy, the method comprising (1) a step of contacting an NMDA-type glutamate receptor with a sample isolated from a subject, and (2) a step of quantifying tau oligomers directly binding to the NMDA-type glutamate receptor.

A soluble N-methyl-D-aspartate receptor (NMDAR) protein construct includes one or more NMDAR autoantibody epitopes. The construct includes an extracellular domain (ECD) of the NMDAR subunit GluN1 or a fragment of the subunit and an ECD of at least one of the NMDAR subunits GluN2A, GluN2B, GluN2C or GluN2D, or fragment of these subunits. An in vitro method for the detection of NMDAR autoantibodies in a sample includes providing a sample suspected of including NMDAR autoantibodies, providing the NMDAR protein construct as a capture molecule, contacting the sample with the NMDAR protein construct, thereby binding NMDAR autoantibodies from the sample to the NMDAR protein construct, and determining the presence and optionally the amount of bound NMDAR autoantibodies. The method is applied for the diagnosis, prognosis, disease monitoring, patient stratification and/or therapy monitoring of a medical condition associated with autoantibodies against the NMDAR, preferably anti-NMDAR encephalitis.

Provided herein are biosensors and methods for detecting one or more odorants associated with the levels, or a change in the levels, of one or more neurotransmitters in the central nervous system of a subject. In embodiments, provided are biosensors that comprise one or more populations of olfactory neurons, or cilia derived therefrom, wherein each population preferentially expresses a specific odorant receptor (OR). Also provided are biosensors comprising a cell or a population of cells engineered to express certain ORs; biosensors comprising certain isolated ORs; transgenic animals and tissues derived therefrom that preferentially express certain ORs; isolated cells or populations of cells engineered to express certain ORs; expression constructs for the preferential expression of certain ORs; and methods of using the biosensors, transgenic animals, tissues, cells, population of cells, and expression constructs disclosed herein.

In various aspects and embodiments the invention provides a method of treating epilepsy in a subject in need thereof, the method comprising providing to the subject an effective amount of an FLNA modulator. In various embodiments, the FLNA modulator is PTI-125 or kartogenin. In various embodiments, the epilepsy is epilepsy associated with focal cortical dysplasia (FCD) type II or tuberous sclerosis complex (TSC).

An assay for Alzheimer's disease (AD) pathology in a living patient is disclosed wherein an amount of α7nAChR or TLR4 in a FLNA-captured protein complex or α7nAChR in an Aβ-captured protein complex or α7nAChR-FLNA, or TLR4-FLNA and/or α7nAChR-Aβ.sub.42 complex present as a protein-protein complex in a sample is compared to the amount in a standard sample from a person free of AD pathology. An amount greater than in the standard sample indicates AD pathology. Also disclosed is an assay predictive of prognosis for treatment with a medicament in which the amount of an above protein or protein complex is compared to an amount in the presence of a medicament that binds to a FLNA pentapeptide and contains at least four pharmacophores of FIGS. 7-12. An amount of protein or protein complex determined in the presence of medicament that is less than the first amount indicates a favorable treatment prognosis.

Human pluripotent stem cells are differentiated in vitro into forebrain subdomain structures, which are then fused to generate an integrated system for use in analysis, screening programs, and the like.

A recombinant, synthetic or monoclonal human antibody or fragment thereof that binds to an N-methyl-D-aspartate Receptor (NMDAR) epitope, which antibody or fragment comprises at least one a heavy chain variable domain sequence encoded by a nucleic acid sequence that is at least 80% identical to SEQ ID NOs. 1, 3, or 5; or at least one a light chain variable domain sequence encoded by a nucleic acid sequence that is at least 80% identical to SEQ ID NOs: 2, 4, or 6. Assays for diagnosis of ANRE employ these NMDAR-binding antibodies, constructs, or epitope binding fragments. In one embodiment, multiple of the NMDAR-binding antibodies or fragments are used as controls because they bind non-overlapping target sequences on the NMDAR ATD.

Provided are Rhipicephalus nicotinic acetylcholine receptors and nucleic acid sequences encoding the same. Provided are furthermore a method of identifying a compound capable of modulating activity of a Rhipicephalus nACh receptor as well as a compound effective in modulating activity of a Rhipicephalus nicotinic acetylcholine receptor.

Agonists and antagonists of nAChRα7 and their use as therapeutic agents for treating and managing inflammatory bowel diseases (IBD), such as Crohn's disease (CD) and ulcerative colitis (UC), are disclosed.