41 results about "Neuron loss" patented technology

The invention relates to methods and products for enhancing and improving recovery of lost memories. In particular the methods are accomplished through the increase of histone acetylation.

The present invention relates to the development of a pharmacological non-human animal model that associates memory loss to histopathological features found in the brain of a subject having Alzheimer's Disease. In one embodiment, a four-week continuous infusion of a Fe2+, Aβ42 and buthionine sulfoximine (FAB) solution in the left ventricle of young adult Long-Evans rats induced memory impairment accompanied by increased hyperphosphorylated Tau protein levels in cerebrospinal fluid. Brains from treated animals displayed neuritic plaques, tangles, neuronal loss, astrogliosis and microgliosis in hippocampus and cortex. The present invention may be utilized in evaluating preventive, therapeutic and diagnostic means for neurologic diseases.

Human mesenchymal stromal cells can be induced to differentiate into oligodendrocytes and neurons, respectively. For these cell types, therefore, MSCs can be a therapeutic source, either in vitro or in vivo, in the context of treating pathologies of the central nervous system which are characterized by neuron loss, such as Parkinson's disease, Alzheimer's disease and stroke, as well as head trauma, or by dysfunction in ganglioside storage or demyelinization, such as Tay-Sachs disease, G1 gangliosidosis, metachromatic leukodystrophy, and multiple sclerosis.

The present invention relates to a method of producing neurons that express the enzyme tyrosine hydroxylase (TH) by subjecting neural stem cells to FGF-1, a protein kinase A activator, a protein kinase C activator, and dopamine / L-DOPA. Surprisingly, when forskolin is used as a protein kinase A activator, it requires only low levels of FGF-1 and forskolin to efficiently produce TH positive neurons from fetal or adult neural stem cells. Also provided are compositions used to produce TH positive neurons and the resulting neural cell culture, as well as a method of treating disease or conditions which are associated with dopamine neuron loss or dysfunction.

The invention relates to methods and products for enhancing and improving recovery of lost memories. In particular the methods are accomplished through the increase of histone acetylation.

The invention relates to methods and products for enhancing and improving recovery of lost memories. In particular the methods are accomplished through the increase of histone acetylation.

Human mesenchymal stromal cells can be induced to differentiate into oligodendrocytes and neurons, respectively. For these cell types, therefore, MSCs can be a therapeutic source, either in vitro or in vivo, in the context of treating pathologies of the central nervous system which are characterized by neuron loss, such as Parkinson's disease, Alzheimer's disease and stroke, as well as head trauma, or by dysfunction in ganglioside storage or demyelinization, such as Tay-Sachs disease, G1 gangliosidosis, metachromatic leukodystrophy, and multiple sclerosis.

Cell suicide (apoptosis) is associated with pathogenesis, for example, it is the major cause for the loss of neurons in Alzheimer's disease. Caspase-3 is critically involved in the pathway of apoptosis. Superantibody (SAT)-trans-membrane technology has been used to produce antibodies against the caspase enzyme in an effort to inhibit apoptosis in living cells. The advantage of using trans-membrane antibodies as apoptosis inhibitors is their specific target recognition in the cell and their lower toxicity compared to conventional apoptosis inhibitors. It is shown that a MTS-transport-peptide modified monoclonal anti-caspase-3 antibody reduces actinomycin D-induced apoptosis and cleavage of spectrin in living cells. These results indicate that antibodies conjugated to a membrane transporter peptide have a therapeutic potential to inhibit apoptosis in a variety of diseases.

This invention discloses the uses of IL-22 in the treatment and prevention of a nerve damage disease or a neurodegenerative disease. In particular, the invention discloses the uses of IL-22 or IL-22 dimers as follows: (i) can protect neurons to recover the functions of injured neurons after ischemic nerve damage in animals in vivo, thus enabling effective treatment of nerve damage diseases, (ii) can significantly inhibit the loss of dopaminergic neurons in substantia nigra in PD model animal, enhance the functions of dopaminergic neurons, significantly reduce neuronal apoptosis in hippocampus, improve learning and memory capacity of AD model rats, and effectively prevent neuronal loss, thereby enabling more effective treatment of neurodegenerative diseases.

The invention discloses application of artemether to prevention and treatment of Alzheimer disease. The artemether is a safe and effective compound in anti-malaria treatment and activates an AMPK signal channel in the brain of an Alzheimer disease transgenic model mouse, the learning and memory ability of the Alzheimer disease transgenic model mouse is improved, apoptosis of nerve cells in the brain is reduced, the function of a choline acetyl transferase is improved, the activity of spongiocyte is inhibited, deposition of amyloid plaques, tangling of nerve fiber and the loss of nerve cells are reduced, and the experimental basis is provided for the clinical study for treating Alzheimer disease.

To treat epilepsy or schizophrenia by transplanting precursor cells of GABAergic neurons into a region where GABAergic neurons are lost or decreased in the brain of a patient suffering from the disease, it is intended to provide a method for separating a precursor cell of GABAergic neuron in an adult or a fetal nerve tissue or a precursor cell of GABAergic neuron derived from an embryo stem cell. The invention of this application comprises the step of preparing a cell population containing a precursor cell of GABAergic neuron, the step of introducing a DNA, in which a reporter gene emitting fluorescence detectable even in vivo is attached to the downstream of a promoter of GAD67 gene or GAD65 gene that is gene of an inhibitory neurotransmitter GABA synthase, into dispersed cells, the step of isolating a GABAergic neuron and a precursor cell of GABAergic neuron based on the presence / absence of the fluorescence from the reporter protein, and the step of isolating the precursor cell of GABAergic neuron based on the possession of proliferative capability.

Disclosed are compounds of formula (1)-(V): where the substituents are as provided herein. Further disclosed are methods of inhibiting tau aggregation, treating or ameliorating a tauopathy or cancer by administration of such a compound. Tau is a microtubule-binding protein that accumulates in a number of neurodegenerative disorders, including frontotemporal dementia and Alzheimer's disease (AD). The presence of abnormal tau correlates with neuron loss and memory deficits in patients with AD and other neurodegenerative disorders that involve tau accumulation.

The present invention concerns methods of using Cathepsin S inhibitors and compounds of Formula I that are inhibitors of cathepsin S in treating CNS disorders, diseases, and injuries, particularly neurodegenerative conditions. The present invention is directed to pharmaceutical compositions comprising these compounds for treating CNS disorders.

The invention discloses an application of a cactus polysaccharide extract to preparing central nervous system injury treating medicine.After a cell proliferation experiment, it is found that by means of the cactus polysaccharide extract, neuronal cell proliferation can be promoted, neuron injuries caused by methylamphetamine can be reduced, mouse neurobehavior disorder caused by the methylamphetamine and learning and memory disorder caused by the methylamphetamine can be improved, neuron losses are reduced, and expression of a nerve growth factor (BDNF) can be improved.In this way, the cactus polysaccharide extract has the quite good protecting effect on neuron injuries, and can be used for treating central nervous system injuries.

The invention discloses use of neuregulin 1, belongs to the technical field of a biomedicine, and particularly relates to application of the neuregulin 1 inpreparation of a drug for treating lead encephalopathy. The characteristics of the lead encephalopathy are high expression of inflammatory cells and inflammatory factors and wide neuronal cell death. Neuron loss and nerve inflammatory reaction play a crucial role in the lead encephalopathy process. The neuregulin 1 has a significant nerve inflammatory reaction and a role of protecting cell apoptosis in the lead encephalopathy, can inhibit inflammatory activation, reduces the quantities of microglial cells and astrocytes, reduces the expression level of inflammatory cytokines COX-2, and improves the learning and memory defects caused by lead poisoning. In addition, the quantity of ErbB4 positive cells can be increased by the neuregulin 1; the inhibition apoptosis activity of anti-apoptosis protein Bc1-2 is improved; expression of pro-apoptotic protein Bax is reduced, so that apoptosis is inhibited, and neuregulin 1 has significant neuroprotective effects on the lead encephalopathy.

The invention belongs to the technical field of medicines and discloses application of a Chuanxiongzine derivative T-006 or a medicinal composition thereof to preparation of a medicine, wherein the medicine is used for preventing and treating nervous system diseases which comprise central nervous system diseases, particularly Parkinson's disease. The action mechanism of the derivative is related to activated MEF2D-PGC1alpha, PI3K-Akt and Nrf2-ARE signal channels, so that dopamine neurons are protected, loss of dopaminergic neurons of substantia nigra pars compacta is reduced, the content of dopamine in striatum is increased and the damaged movement function of patients is improved. When the derivative and the medicinal composition thereof is used for preparing the medicine for preventing and treating the nervous system diseases, the derivative and the medicinal composition thereof as well as useable medicine carriers can be prepared into various dosage forms, and the derivative and themedicinal composition thereof can be used in combination with other related medicines.

The invention relates to the fields of medicines and foods, in particular to application of astragalus smicus glycoside in resisting aging and inflammation aging. According to the application of astragalus smicus glycoside in resisting aging and inflammation aging, animal tests and cellular level tests show that the astragalus smicus glycoside has the effects of resisting aging, improving cognition, learning and memory ability, inhibiting glial cell activation and neuron loss, and reducing central and peripheral inflammation aging level and oxidative stress level. The research on the anti-aging effect of the astragalus smicus glycoside on a D-galactose / aluminum chloride aging model (hereinafter referred to as a D-Gal model) mouse finds that the astragalus smicus glycoside can be used for preparing an anti-aging product.

The invention discloses application of an NRG (neuregulin) 1beta1 / ErbB4 / Akt signal pathway in preparing or screening a drug target for resisting Alzheimer disease neuronal loss. Experiments discover the protection effect of the NRG1beta1 / ErbB4 / Akt in resisting neuronal loss in Alzheimer disease, the application firstly provides that NRG1beta1 plays the occurrence development process of resisting apoptosis in brain of Alzheimer disease by activating an ErbB4 receptor in brain, and a more specific novel target is provided to effective prevention, control or treatment of Alzheimer disease.

The present invention provides a compositions and methods for prevention and prophylaxis of neurological diseases accompanied by neuronal death. The invention includes synthesis of 5-benzylamino salicylic acid (BAS) and its derivatives. BAS and its derivatives protect cortical neurons from toxic insults by N-methyl-D-aspartate, Zn2+, and reactive oxygen species. Thus, the present invention provides compositions and methods for treating stroke, traumatic brain and spinal cord injury, epilepsy, and neurodegenerative diseases that are accompanied by severe neuronal loss via excitotoxicity, Zn2+ neurotoxicity, and free radical neurotoxicity.

The invention discloses a function application of SH2B adapter protein 1 in treating Parkinson's disease. Through neuron-specific over-expression of the SH2B1, dopaminergic neuron loss of substantia nigra pars compacta in an MPTP-induced mouse can be obviously improved, and the level of dopamine in striatum can be increased; and the proliferation and the activation of astrocytes and microglia of the substantia nigra pars compacta can be inhibited. Based upon the research results, it is indicated that the SH2B1 can be used for preparing medicines for treating the Parkinson's disease. Accordingto the invention, the therapeutic effect of the SH2B1 in the Parkinson's disease is verified for the first time; therefore, the SH2B1 is huge in market value and social benefit.

Evidence indicates dysregulation. of the immunoregulatory molecule CD45 occurs in Alzheimer's disease (AD). Transgenic mice overproducing amyloid-β peptide (Aβ) and deficient in CD45 (PSAPP / CD45− / −) recapitulate AD neuropathology. Increased cerebral intracellular and extracellular soluble oligomeric and insoluble Aβ, decreased plasma soluble Aβ increased microglial neurotoxic cytokines TNF-α and IL-1β, and neuronal loss were found in PSAPP / CD45− / − mice compared with CD45-sufficient PSAPP littermates. After CD45 ablation, in vitro and in vivo studies demonstrate a microglial phenotype whereby microglia phagocytose less Aβ but display proinflammatory properties. This microglial activation occurs with elevated Aβ oligomers and neural injury and loss as determined by decreased ratio of anti-apoptotic Bcl-xL to proapoptotic Bax, increased activated caspase-3, mitochondrial dysfunction, and loss of cortical neurons in PSAPP / CD45− / − mice. These data show that deficiency in CD45 activity leads to brain accumulation of neurotoxic Aβ oligomers and validate CD45-mediated microglial clearance of oligomeric Aβ as a novel AD therapeutic target.

The present invention relates to a novel crystalline acid salt of a tricyclic derivative or a hydrate thereof and a production method thereof. The crystalline acid salt or the hydrate thereof according to the present invention is stable with respect to humidity and stable with respect to hygroscopicity, and the quality control during manufacturing drugs is favorable. In addition, the crystalline acid salt or the hydrate thereof may be used in a pharmaceutical composition for preventing or treating neuropathic pain, epilepsy, stroke, Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis (ALS), Huntington's disease, schizophrenia, chronic and acute pain, ischemic brain injury, neuronal loss after hypoxia, trauma and nerve damage, which are medical conditions induced by PARP overactivity.

A composition for preventing nervous diseases accompanied with neuron death, its method and synthesis of BAS and its derivative are disclosed. BAS and its derivative prevent cortical neuron from being damaged by N-methyl-D-aspartate, zinc ion and active oxide cluster. It can be used to treat apoplexia, cerebral traumatism, spinal injury, epilepsy and other neurodegenerative diseases, which accompany with serious neuron lost.

The invention provides a nano sustained-release preparation, which belongs to the technical field of nano materials. The nano sustained-release preparation provided by the present invention comprises dextran-modified cerium oxide nanoparticles and silk fibroin coated on the outer layer of the dextran-modified cerium oxide nanoparticles. In the present invention, cerium oxide nanoparticles coated with dextran have good water-soluble dispersibility, and have excellent antioxidant activity and oxygen-carrying capacity, which can significantly improve neuron loss caused by hypoxia and oxidative damage, and restore mitochondria The morphology and structure of silk fibroin have good biocompatibility, and the use of silk fibroin to coat dextran-modified cerium oxide nanoparticles can achieve the effect of slow release of nanoparticles, avoiding the shortcomings of instantaneously high drug concentration and rapid metabolism; At the same time, silk fibroin is biodegradable, and its degradation products are safe and pollution-free.

The invention discloses the application of simulated fasting diet in preventing and treating Parkinson's disease, and belongs to the technical field of medical neurology. After establishing a Parkinson's disease animal model, the present invention comprehensively uses various research methods such as behavioral, immunological, biochemical indicators, etc., and experiments confirm that the drug can improve the movement disorder symptoms of Parkinson's disease model mice; reduce dopamine in the substantia nigra pars compacta neuron loss. The simulated fasting diet has strong operability and good effect, so it has certain development value and prospect in clinical application.

The present invention concerns methods of using Cathepsin S inhibitors and compounds of Formula I that are inhibitors of cathepsin S in treating CNS disorders, diseases, and injuries, particularly neurodegenerative conditions. The present invention is directed to pharmaceutical compositions comprising these compounds for treating CNS disorders.

The present invention relates to the development of a pharmacological non-human animal model that associates memory loss to histopathological features found in the brain of a subject having Alzheimer's Disease. In one embodiment, a four-week continuous infusion of a Fe2+, Aβ42 and buthionine sulfoximine (FAB) solution in the left ventricle of young adult Long-Evans rats induced memory impairment accompanied by increased hyperphosphorylated Tau protein levels in cerebrospinal fluid. Brains from treated animals displayed neuritic plaques, tangles, neuronal loss, astrogliosis and microgliosis in hippocampus and cortex. The present invention may be utilized in evaluating preventive, therapeutic and diagnostic means for neurologic diseases.