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.

The present invention relates to bifunctional compounds, which find utility as modulators of targeted ubiquitination, especially inhibitors of a variety of polypeptides and other proteins which are degraded and/or otherwise inhibited by bifunctional compounds according to the present invention. In particular, the present invention is directed to compounds, which contain on one end a VHL ligand which binds to the ubiquitin ligase and on the other end a moiety which binds a target protein such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of that protein. The present invention exhibits a broad range of pharmacological activities associated with compounds according to the present invention, consistent with the degradation/inhibition of targeted polypeptides.

An object of the present invention is to provide a compound having an anti-inflammatory activity or a pharmacologically acceptable salt thereof. The solution of the present invention is a compound of general formula (1) or a pharmacologically acceptable salt thereof. ##STR00001##
wherein the symbols in the formula are defined below:
A: e.g., Benzene, E: e.g., —CH.sub.2—, G: e.g., a 5-membered aromatic heterocyclic ring, X: e.g., cyclohexane, J: e.g., a 5-membered aromatic heterocyclic ring, Y: e.g., a phenyl group, R.sup.1, R.sup.2, R.sup.3: e.g., a halogen atom, R.sup.4: e.g., a C1-C6 alkyl group, R.sup.5: e.g., a hydrogen atom, R.sup.6a, R.sup.6b, R.sup.6c, R.sup.6d: e.g., a hydrogen atom, R.sup.7: e.g., a hydrogen atom, R.sup.8: e.g., a hydrogen atom, n.sup.1, n.sup.2, n.sup.3: e.g., 1.

Anti-alpha-synuclein antibodies and antigen-binding fragments thereof (e.g., scFvs) are provided. Also provided are methods of using the same in therapy.

Anti-alpha-synuclein antibodies and antigen-binding fragments thereof (e.g., scFvs) are provided. Also provided are methods of using the same in therapy.

The purpose of the present invention is to provide a novel medical application of pluripotent stem cells (muse cells) in regeneration medicine. The present invention provides a cell preparation and a pharmaceutical composition which are for amelioration and treatment of brain disorders resulting from fetal growth retardation, such as abnormal motor quality or abnormal neurological development, and which contain SSEA-3 positive pluripotent stem cells isolated from a mesenchymal tissue from a live body or cultured mesenchymal cells. It is assumed that this cell preparation is based on a mechanism where muse cells that are administered to objects having the disorders are engrafted on an impaired brain tissue, thereby ameliorating or treating the disorders.

The purpose of the present invention is to provide a novel medical application of pluripotent stem cells (muse cells) in regeneration medicine. The present invention provides a cell preparation and a pharmaceutical composition which are for amelioration and treatment of brain disorders resulting from fetal growth retardation, such as abnormal motor quality or abnormal neurological development, and which contain SSEA-3 positive pluripotent stem cells isolated from a mesenchymal tissue from a live body or cultured mesenchymal cells. It is assumed that this cell preparation is based on a mechanism where muse cells that are administered to objects having the disorders are engrafted on an impaired brain tissue, thereby ameliorating or treating the disorders.

The invention discloses a substituted pyrazole compound of formula (I), preparation method therefor, a pharmaceutical composition and a medical use thereof. The said compound features excellent stability, solubility, and low cytotoxicity, which is significantly beneficial for neurological protection, effectively preventing and treating nerve cell injuries. It is an ideal pharmaceutical compound for preventing or treating stroke, cerebral embolism, stroke sequelae, stroke-related motor dysfunction, mitochondrial encephalomyopathy, and amyotrophic lateral sclerosis.

##STR00001##

The subject matter generally relates to methods of treatment and/or prophylaxis of CNS diseases, disorders, and/or injuries. In one aspect, the subject matter relates to inhibitors of phosphodiesterase 1 (PDE1) as neuroprotective agents and/or neural regenerative agents. In a further aspect, the subject matter relates to individuals that are at risk for the development of CNS disease or disorder.

The subject matter generally relates to methods of treatment and/or prophylaxis of CNS diseases, disorders, and/or injuries. In one aspect, the subject matter relates to inhibitors of phosphodiesterase 1 (PDE1) as neuroprotective agents and/or neural regenerative agents. In a further aspect, the subject matter relates to individuals that are at risk for the development of CNS disease or disorder.