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.

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.

The serotonin receptor 5HT2A (5HT2aR) and membrane NADPH oxidases (NOX enzymes) are found to be a target of autoantibodies present in Multiple Sclerosis patients. The present invention refers to peptides comprised in the extracellular regions of the human 5HT2aR and/or NOXs for diagnosis and therapy of Multiple Sclerosis.

A method for treating a subject with depression characterized by having an increased burst firing in neurons of a lateral habenula in the subject is provided. The method includes a step of administering to the subject a pharmaceutical composition capable of inhibiting the burst firing in the lateral habenula of the subject. The pharmaceutical composition includes one or more active pharmaceutical agents, which can suppress the burst firing in the lateral habenula of the subject and can include at least one of an N-methyl-D-aspartate receptor (NMDAR) inhibitor or a T-type calcium channel inhibitor. The pharmaceutical composition can be in a formulation allowing for local administration to the lateral habenula of the subject, or can be in a formulation configured for systemic administration to the subject. A method for testing a test substance for an antidepressive effect is also provided.

The present disclosure relates to a pharmaceutical composition for inducing an exercise mimetic effect, which contains an .sub.1-adrenergic receptor agonist as an active ingredient, and a method for screening a drug for inducing an exercise mimetic effect using the .sub.1-adrenergic receptor agonist.

The .sub.1-adrenergic receptor agonist of the present disclosure increases the expression of p-AMPK, PPAR and PGC-1, which play key roles in maintaining and regulating energy metabolic activity in vivo, thereby increasing glucose uptake into skeletal muscle cells, suppressing adipocyte differentiation and lipid accumulation, reducing abdominal fat and body weight as well as regulating mitochondrial metabolic disorders and suppressing inflammatory responses. Accordingly, the .sub.1-adrenergic receptor agonist can be usefully used to prevent and treat diseases requiring AMPK activation (metabolic diseases, cardiovascular diseases, inflammatory disease, etc.).

A method for diagnosing Alzheimer's disease (AD) includes: obtaining a blood sample from a human subject suspected of having AD; determining a G72 protein level in the blood sample; determining an SLC7A11 mRNA expression level in the blood sample; comparing the G72 protein level with a first predetermined standard; comparing the SLC7A11 mRNA expression level with a second predetermined standard; and diagnosing the human subject with AD when the G72 protein level is higher than the first predetermined standard and the SLC7A11 mRNA expression level is higher than the second predetermined standard. An effective amount of a pharmaceutical composition may be administered to the diagnosed human subject for treating AD.

A method of inhibiting phosphorylation of the tau protein and/or a TLR4-mediated immune response is disclosed. The method contemplates administering to cells in recognized need thereof such as cells of the central nervous system an effective amount of a of a compound or a pharmaceutically acceptable salt thereof that binds to a pentapeptide of filamin A (FLNA) of SEQ ID NO: 1, and contains at least four of the six pharmacophores of FIGS. 35-40.

The invention provides the use of circulating astrocytes (cAstr) and the Major Facilitator Superfamily Domain containing Protein 2a (Mfsd2a) as biomarkers, and their combined use with other related circulating markers (cBMEC and EPC) in early detection and diagnosis of cerebrovascular diseases (CVD) or central nervous system (CNS) disorders.

An assay for Alzheimer's disease (AD) pathology in a living patient is disclosed wherein an amount of 7nAChR or TLR4 in a FLNA-captured protein complex or 7nAChR in an A-captured protein complex or 7nAChR-FLNA, or TLR4-FLNA and/or 7nAChR-A.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.

The invention provides the use of circulating astrocytes (cAstr) and the Major Facilitator Superfamily Domain containing Protein 2a (Mfsd2a) as biomarkers, and their combined use with other related circulating markers (cBMEC and EPC) in early detection and diagnosis of cerebrovascular diseases (CVD) or central nervous system (CNS) disorders.