According to a production method for a brain organoid, comprising a step 1 of carrying out suspension culture of human pluripotent stem cells having a mutation in at least one or more base sequences in an exon selected from the group consisting of an exon 9, an exon 10, an exon 11, an exon 12, and an exon 13 of a microtubule-associated protein tau (MAPT) gene, and having a mutation in at least one or more base sequences in an intron 10 of the MAPT gene, it is possible to produce a brain organoid having a phosphorylated 3-repeat tau protein and a phosphorylated 4-repeat tau protein.

The present invention relates to a method of preparing induced neural stem cells which are reprogrammed from differentiated cells. The method of producing the induced neural stem cells according to the present invention enables preparation of the induced neural stem cells from non-neuronal cells using only two inducing factors of SOX2 and HMGA2. Therefore, the method of the present invention can prepare induced neural stem cells in a more efficient manner than the conventional methods, which use four or five inducing factors. Additionally, the method of the present invention shows significantly higher inducing efficiency and proliferation capacity than when only a single SOX2 gene is used, thus increasing its potency to be used for therapeutic purposes.

Techniques and systems are disclosed for a bioassay that is an in vitro mimic of peripheral nerve generation using the sensory neurons that innervate the peripheral nervous system. In some embodiments, the techniques may assist in detecting the bioactivity or potency of nerve grafts (e.g., processed, acellular human allografts) for fostering or supporting peripheral nerve regeneration. In various embodiments, techniques comprise affixing neurons (e.g., a DRG) to a nerve graft segment to form a test construct; culturing the test construct in a medium; analyzing the test construct to indicate the amount of outgrowing nerve structure; and determining the potency of the nerve graft from a metric derived from the analysis. In some embodiments, techniques and materials may be used to test the effect of a varied test condition on nerve growth.

A peptide is described herein that has: (i) a simple structure compared to existing natural human erythropoietin, thus capable of easily passing through a tissue-blood barrier, (ii) excellent bioactivity with respect to cell-protecting activity, (iii) a low manufacturing cost, thus being economically advantageous, and (iv) no side effects on cell proliferation. Also, a pharmaceutical composition comprising the erythropoietin-derived peptide described herein as an active ingredient is described. The pharmaceutical composition may be used for preventing or treating cell damage-related illnesses, such as stroke, mechanical damage or ischemic damage to the nervous system, myocardial infarction, retinal damage, and diabetes. Also, the described pharmaceutical composition may be used for preventing cell damage.

Nonsense-mediated mRNA decay (NMD) polypeptides, nucleic acids encoding NMD polypeptides, and methods of using such polypeptides and nucleic acids in the treatment of ALS and in screening for agents for the treatment of ALS are described.

The present invention is directed to a system including neurons over-expressing UBB+1, organized in a 3-dimensional culture, and method of using same. A process for making the system of the invention is also provided.

Genetically encoded calcium indicator (GECI) polypeptides and the nucleic acid molecules encoding such polypeptides are provided.

The instant invention provides methods and compositions related to discovery of Free Fatty Acid Receptor 1 (FFA1) as a therapeutic target for treatment or prevention of diseases or disorders of neurons that are characterized by angiogenesis, or of vascular diseases of the eye, retinal degeneration and/or tumors more generally. Therapeutic and/or prophylactic uses and compositions of known FFA1 inhibitors, including small molecules and nucleic acid agents, are described. Methods for identification of novel FFA1 inhibitors are also provided.

The invention relates to a genetically modified mouse comprising a heterozygous mutation of Tardbp (TDP-43) gene in that the Asn at amino acid 390 in TDP-43 is substituted with an amino acid that is different from Asn, wherein the genetically modified mouse exhibits Amyotrophic lateral sclerosis (ALS)-like phenotypes, TDP-43 proteinopathies and/or motor neuron degeneration. The invention also so relates to an isolated spinal cord motor neuron differentiated from an embryonic stem cell (ESC) that is obtained from an offspring of a genetically modified mouse according to the invention. Methods for identifying an agent alleviating and/or suppressing ALS-TDP pathogenesis are also disclosed.

Disclosed herein is an agent that modulates a cis interaction between Repulsive Guidance Molecule A (RGMa) and Neogenin or lipid rafts. Modulation by the agent may include blocking the cis interaction between RGMa and Neogenin and/or disrupting lipid rafts. In turn, this promotes neuronal cell survival and axon growth and/or regeneration. Also disclosed herein is a method of treating a disease in a subject in need thereof. The method may include administering the agent to the subject. Further disclosed herein is a method of identifying an agent that modulates the cis interaction between RGMa and Neogenin.