The present invention is directed to a method for identifying a gene that regulates clostridial neurotoxin activity, the method comprising: a. providing a sample of human neuronal cells expressing a polypeptide that comprises a C-terminal detectable label, wherein the polypeptide is cleavable by a clostridial neurotoxin; b. altering expression of a target gene of the cells; c. contacting the cells with the clostridial neurotoxin; d. measuring an amount of C-terminal detectable label, thereby quantifying clostridial neurotoxin activity; and e. identifying the target gene as a regulator of clostridial neurotoxin activity when the quantified clostridial neurotoxin activity is different to the quantified clostridial neurotoxin activity when expression of the target gene is unaltered; or f. identifying that the target gene is not a regulator of clostridial neurotoxin activity when the quantified clostridial neurotoxin activity is equivalent to the quantified clostridial neurotoxin activity when expression of the target gene is unaltered. Also provided are related methods for identifying an agent that regulates clostridial neurotoxin activity, as well as human neuronal cells, nucleotides, vectors, polypeptides, kits, and compositions suitable for use in the methods of the invention.

Provided are an odorant receptor marker of microglia and a use thereof, and according to the odorant receptor marker of microglia and a use thereof according to one aspect, microglia may be detected by measuring an activity or expression level of a protein of an odorant receptor (OR) Olfr110 or Olfr111, and OR ligands of microglia may be selected using them, and an inhibitor or activator against the interaction between the OR and 2-pentylfuran is effectively used in treatment of a neuroinflammatory disease or meningitis.

The present invention provides methods and systems using optogenetic assays to identify features in measured neuronal action potentials that can be used to characterize neural disorders and potential therapeutic treatments.

The present invention provides compositions exhibiting in vivo activity of fibrin in an in vitro setting, in vitro assays comprising such compositions, methods of producing such compositions, and methods of using such compositions and assays. The compositions of the invention include molecules with the biochemical properties of 1) high affinity binding to fibrin receptors and 2) activation of cell-signaling systems comparable to that observed in vivo by fibrin. The fibrin compositions of the invention are compatible both in biochemical assays and cell-based assays, and thus useful for in vitro assays for screening of test agents that modulate cell activation and/or signaling pathways mediated by fibrin or associated with fibrin activity.

Methods of determining the suitability of a subject for treatment with a therapeutic agent are provided. Methods of providing a personalized treatment protocol based on suitability of a subject to be treated with a therapeutic agent are also provided, as are methods of treating those subjects who are suitable.

The disclosure provides methods for rescuing synaptic defects caused by abnormal MeCP2 expression in a subject in need thereof, comprising administering to the subject therapeutically effective amount(s) of a nootropic agent and/or an alpha-7 nicotinic acetylcholine receptor (α7-nAChR) agonist. The disclosure further provides methods for screening candidate drug candidates in a tiered series of assays and models (neurons, MECP2-mosaic neurospheres, and cortical organoids).

The present invention addresses a problem of providing a method for collecting extracellular vesicles derived from nervous system cells at an improved efficiency.

This problem is solved by a method for collecting extracellular vesicles derived from nervous system cells, said method comprising a step for mixing an anti-APLP1 antibody with a sample containing extracellular vesicles to form anti-APLP1 antibody-extracellular vesicle complexes and a step for collecting the anti-APLP1 antibody-extracellular vesicle complexes.

Compositions and methods are provided for biologically relevant in vitro screening of neural function, including determination of the effects of an agent on neural cells. The compositions of the invention useful in such screening methods include a neural co-culture system comprising human pluripotent stem cell (PSC)-derived neurons and human glial cells, which may be derived by culture methods allowing for rapid and robust development of highly mature neuronal activity, particularly spontaneous synchronous network bursts.

Human raphe nuclei organoids or spheroids (hRNS) are generated in vitro, which may be generated at least in part from human pluripotent stem (hPS) cells. Such spheroids model the human raphe nuclei and comprise specific sets of cells, e.g. serotonergic neurons, that are associated with the raphe nuclei of a human, and can be assembled with cortical spheroids (hCS) to generate functional human neuromodulatory circuits.

The invention relates to modeling brain neuronal disease in a microfluidic device, comprising a co-culture of iPS-derived brain endothelial cells; iPS-derived dopaminergic neurons; primary microglia; and primary astrocytes, a Blood-Brain-Barrier (BBB)-Chip and a Brain-Chip. In particular, cross-talk between glial cells (e.g. microglia and astrocytes) with neuronal cells, in further contact with endothelial cells is contemplated for use for identifying drug targets under conditions for inducing in vivo relevant neuronal inflammation, neurodegeneration and neuronal death. Thus, in one embodiment, a microfluidic Brain-Chip comprising a co-culture of brain cells is exposed to α-synuclein preformed fibrils (PFF), a type of pathogenic form of α-synuclein. Such α-synuclein PFF exposure demonstrates an in vivo relevant disease pathogenesis on a microfluidic device as a concentration- and time-controlled manner that may be used for preclinical drug evaluation for diseases related to neuronal inflammation, e.g. Parkinson's disease (PD). In some embodiments, modulation of complement in the presence of neuronal inflammation is contemplated. In some embodiments, drug delivery to brain cells across the BBB is contemplated for preclinical testing of drug efficacy for slowing or stopping neuronal inflammation and degeneration.