62 results about "Neuronal apoptosis" patented technology

The present invention relates to novel neurosteroid derivatives with anti-apoptotic, neuroprotective and neurogenic properties that act on the nervous system as well as methods for making the same and their applications in the treatment and / or prevention or amelioration of neurodegenerative diseases related to neuronal apoptosis or neuronal injury, or conditions related to or resulting from apoptosis, including but not limited to Alzheimer's disease, Parkinson's disease, Huntington's disease, multiple sclerosis and amyotrophic lateral sclerosis (ALS), retinal degeneration and detachment, peripheral neuropathy caused by genetic abnormalities, diabetes, polio, herpes, AIDS and chemotherapy, brain trauma, or ischemia and stroke. The active compounds are represented by Formula (I): wherein R1, R2, R3, R4, R5, R6, R7, A, B, X, Y and Z are defined in the description of the invention. The present invention also includes compositions which comprise one or more of the compounds of Formula (I).

Provided are methods for protecting against or reducing neurotoxicity of exposure to a neurotoxic agent, comprising administering an electrokinetically altered aqueous fluid as provided herein in an amount sufficient to provide for neuroprotection against the neurotoxic agent, preferably where protecting against or reducing loss of motor coordination in the subject exposed to the neurotoxin is afforded. In certain aspects, protecting or reducing neurotoxin-mediated neuronal apoptosis is afforded, and / or activating or inducing at least one of PI-3 kinase and Akt phosphorylation in neurons is afforded. Preferably, administering the fluid comprises administering the fluid prior to exposure to the neurotoxic agent. Additionally provided are methods for preserving or improving motor coordination in a subject having a neurodegenerative condition or disease, comprising administering an electrokinetically altered aqueous fluid as provided herein in an amount sufficient to provide for preserving or improving motor coordination in the subject.

The invention discloses a micro-molecule polypeptide TAT-p53DM and an application thereof to preparing a medicine for treating or preventing ischemic stroke. A fusion protein polypeptide TAT-p53DM of a TAT protein transduction domain and p53DM is artificially synthesized; TAT carries p53DM protein polypeptide to pass through a blood brain barrier through blood so as to be taken by nerve cells; used in an in-vitro and in-vivo ischemic stroke model, the micro-molecule polypeptide TAT-p53DM is capable of effectively playing a biological role in blocking binding between death domain of death associated protein kinase 1 (DAPK1DD) and tumor suppression protein p53DNA binding motifs (p53DM), inhibiting signals capable of causing neuronal apoptosis and necrosis at DAPK1 downstream, and reducing ischemic stroke brain injury; moreover, molecular targets are provided for further developing medicines for clinically treating ischemic stroke.

The invention relates to a method of treating neuronal apoptosis in a mammal using nucleic acid encoding HSV-2 ICP10PK, or a polypeptide encoded thereby. The invention further relates to a method of treating neuronal apoptosis in a mammal using ICP10PK in combination with a nucleic acid encoding bcl-2, or the polypeptide encoded thereby. The invention also relates to the use of ICP10PK and ICP10PK in combination with bcl-2 to treat non-neuronal diseases characterized by apoptosis.

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 present invention relates generally to methods for inhibiting neuron apoptosis and necrosis associated with excess glutamate release.

The present invention relates to a method for treating a brain injury due to a traumatic event, disease or ischemic attack in a mammal subject, wherein the method comprises administering to the mammal subject an effective amount of miR-23a-3p and / or miR-27a-3p mimics to reduce activation of Puma, Noxa and Bax therby causing a subsequent reduction in neuronal apoptosis.

The invention relates to an apparatus for treating a bodily lesion that is associated with inadequate blood perfusion, partial denervation, neuronal apoptosis, tissue loss, pain, oedema and / or infection. The inventive apparatus is used to apply external, non-invasive, analgesic electromagnetic fields (EMF) to the patient with the lesion, in an area removed from the site of the lesion. The aforementioned electromagnetic fields are effective in increasing angiogenesis, vasculogenesis, neural tissue regeneration and osteogenesis, restoring the wound repair process, providing analgesic, anti-oedema, anti-inflammatory effects and / or repairing wounds. The electromagnetic fields include frequencies from several Hertz up to less than approximately 300 Hz, as well as components of a static field from between several microteslas and a maximum intensity of between approximately 0.3 and approximately 0.8 mT, which can be applied alone or together with a homogeneous static field from approximately 40 to approximately 80 T, or approximately 400 to approximately 800 Gauss.

The invention discloses a centella extract. The preparation method comprises the following steps: with an ethanol solution as a solvent, carrying out crude extraction on centella by using an ultrasonic extraction method; and with an AB-8 resin separation column and the ethanol solution as eluents, separating out effective components, wherein the target components eluted by 30%-50% of ethanol and 51%-75% of ethanol solution are the centella extracts. The centella extract disclosed by the invention is capable of promoting cell proliferation and differentiation of a neuron model PC12 without NFG induction, and can be applied to treatment of depressive disorder, and related diseases of various nerve injuries and neuronal apoptosis. The extraction method provided by the invention is simple in process, low in cost and high in efficiency.

The present invention discloses a chrysotoxine bibenzyl derivative shown as a formula I. R1 represents C=O, CH2, NH, S=O or a covalent bond; R2 represents alkyl, phenyl, substituted phenyl, benzene ring substituted C1-3 alkyl, C5-C6 cycloalkyl, and a pentabasic or hexahydric unsaturated heterocyclic group containing one or more O, S and N. The invention also discloses a simple and efficient preparation method of the chrysotoxine bibenzyl derivative, and application of the derivative to the preparation of neuroprotective drugs and drugs for treating Alzheimer disease. The chrysotoxine 4-O-substituted bibenzyl derivative has significant protective effect on A beta-induced neuronal apoptosis, and is a potential novel chemical entity for the treatment of AD.

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 present invention relates to a pharmaceutical composition for protecting neurons or for preventing and treating ischemic neuronal diseases comprising the extract of Lithospermum erythrorhizon Sieb. Et Zucc extracted with water, low-alcohols or their mixture or acetylshikonin separated therefrom as an effective ingredient. The extract of Lithospermum erythrorhizon Sieb. Et. Zucc or acetylshikonin separated therefrom of the present invention has neuronal protective effect, so that it not only interrupts the development of ischemic neuronal diseases but also is very safe, indicating that the extract or acetylshikonin can be used as a medicinal drug for prevention and treatment of degenerative brain disease caused by neuronal apoptosis such as stroke, apoplexy, dementia, Alzheimer's disease, Parkinson's disease, Huntington's disease, Pick's disease and Creutzfeldt-Jakob disease and further can be developed as functional health food.

The invention discloses application of DPP4 inhibitors to preparation of drugs used for preventing and treating epilepsy, belonging to the field of medical application. The DPP4 inhibitors are applied to prolong the incubation period of epilepsy of rats, shorten duration time of epilepsy, reduce the grade of attack, lower the amplitude and frequency of abnormal discharge of nerve cells, alleviate neuronal damage of rats with epilepsy, improve neuronal apoptosis of rats with epilepsy, and decrease neuronal degeneration and necrosis of rats with epilepsy. The DPP4 inhibitors in the invention are approved clinical medicines; and the DPP4 inhibitors are definite in active ingredients and curative effect, low in toxic and side effect and long in duration time of drug effect and can reduce cost for research and development of the drugs.

The invention relates to the technical field of medicine, in particular to an application of a bFGF (basic Fibroblast Growth Factor) to preparation of a medicament for treating human ischemic stroke. During the application of the bFGF (basic Fibroblast Growth Factor) to preparation of the medicament for treating human ischemic stroke, the medicament can be in the forms of a powder injection, a water aqua, a lipoplast and the like. The bFGF can be used of treating ischemic stroke; and a small dosage of bFGF can be used for inhibiting endoplasmic reticulum stress, reducing neuronal apoptosis caused by endoplasmic reticulum, and has a treatment effect on ischemic stroke.

The invention provides application of mesenchymal stem cell derived extracellular vesicles to cerebral ischemia-reperfusion injury. Research of the invention finds and verifies that extracellular vesicles (MSCs-EVs) derived from mesenchymal stem cells are capable of treating disordered brain functions and taking a neuroprotective effect into play through neurogenesis and angiogenesis after stroke.Research results show that within 24 hours and 48 hours after MCAO (middle cerebral artery occlusion), MSCs-EVs are capable of remarkably reliving neurologic impairment of rats, reducing the volume of cerebral infarction and brain water contents, relieving pathological injury of brain tissue cortexes, weakening cortex neuronal apoptosis, remarkably increasing p-AMPK (protein kinase), and reducingp-JAK2, p-STAT3 and p-NF-kB. Due to the application, essential support is provided for potential treatment strategies of MSCs-EVs as MCAO treatment.

The present invention provides methods for preventing or reducing neuronal apoptosis, particularly wherein the apoptosis is associated with a neurodegenerative disorder in a subject.

The invention discloses a medicinal and edible dual-purpose composition for preventing and treating vascular dementia and a preparation method thereof, belonging to the fields of food therapy and preparation of health products and traditional Chinese medicines. An optimal dosage form of a composition product is a soft capsule dosage form, and the medicinal and edible dual-purpose composition comprises the following components in parts by weight: 10-18 parts of a seabuckthorn seed procyanidine extract, 4-11 parts of a seabuckthorn flavone extract, 8-18 parts of a longstamen onion bulb extract and 63-72 parts of seabuckthorn seed oil. A preparation method of a soft capsule comprises the following steps: firstly preparing inclusions in the capsule into oil powder suspensions, and then preparing the oil powder suspensions into the soft capsule dosage form. The components of the medicinal and edible dual-purpose composition are all medicinal and edible dual-purpose varieties, are safe, and can be taken for a long time. The medicinal and edible dual-purpose composition disclosed by the invention can be used for effectively reducing the platelet aggregation rate and blood viscosity and increasing the cerebral blood flow, has extremely strong free radical removal and anti-oxidation effects, can be used for reducing the generation rate of MDA, repairing and protecting cranial nerve injury, and inhibiting hippocampal neuronal apoptosis, and plays roles in effectively preventing vascular dementia and treating vascular dementia.

The present invention relates to a method for treating a brain injury due to a traumatic event, disease or ischemic attack in a mammal subject, wherein the method comprises administering to the mammal subject an effective amount of miR-23a-3p and / or miR-27a-3p mimics to reduce activation of Puma, Noxa and Bax therby causing a subsequent reduction in neuronal apoptosis.

The invention provides the application of miR-21 in the diagnosis and treatment of subarachnoid hemorrhage, and belongs to the technical field of biomedicine and molecular biology. According to the application of miR-21 in the diagnosis and treatment of subarachnoid hemorrhage, the potential therapeutic effects of mesenchymal stem cell exosomes in SAH are explored, particularly in the effect on cognitive function. It is proved that the mesenchymal stem cell exosomes can reduce early brain damage after SAH and improve the cognitive function. In the mechanism, it is demonstrated by the exosomesrich in miR-21 play an important role in mediating effect on inhibiting neuronal apoptosis. According to the application of miR-21 in the diagnosis and treatment of subarachnoid hemorrhage, it is actually proved that miR-21 in the mesenchymal stem cell exosomes reduces brain damage after SAH by inhibiting the neuronal apoptosis, the neural behavior is improved through a PTEN / Akt pathway, potentialnovel restorative treatment methods and strategies are provided for SAH patients with the risk of cognitive deficits, and thus the good practical application value is obtained.

The invention relates to the technical field of pharmaceutics and discloses the application of the compound AM-1241, namely (R,S)-3-(2-iodo-5-nitrobenzene formyl)-1-(1-methyl-2-piperidinyl methyl)-1H-indol to preparation of a drug for treating Parkinson's disease. According to the compound, a cannabinoid receptor CB2 is used as the effective target spot of Parkinson's disease treatment, and symptoms of Parkinson's disease can be relieved greatly; furthermore, a molecular mechanism shows that CB2 expression of substantia nigra and hippocampus are activated, the occurrence rate of neuronal apoptosis is reduced, and a remarkable neuroprotective effect is realized; besides, by preparing the compound into solid lipid nanoparticle preparations for administration, drug absorption rate and brain-targeting effect can be improved, so that Parkinson's disease treatment effect is further improved. It is expected to prepare the drug for treating Parkinson's disease with the compound as the effective constituent, and the drug can become the substitution of existing levodopa drugs.

The invention relates to a polypeptide derived from the TSR (thrombospondin type 1 units) of SCO-Spondin for inhibiting or preventing the apoptosis mediated by the cell death receptor ligands, such as TRAIL or FasL. The polypeptide of the invention comprises a sequence -W-S-A1-C-S-A2-C-G- wherein A1 and A2 are amino acid sequences comprising 1 to 5 amino acids. More particularly, the invention relates to said polypeptide for inhibiting or preventing the apoptosis associated with a disease selected from the group consisting of neurodegenerative disorders, cerebral ischemia, neuronal traumas, neuronal inflammatory diseases, and viral neurodegenerations.

The invention discloses medical application of a catalpol and / or radix astragali seu hedysari extraction solution. Experiments show that the catalpol and / or radix astragali seu hedysari extraction solution can be used for preventing and treating or delaying motor neuron diseases and nerve injury. Results show that through injection of a catalpol injection solution, a radix astragali seu hedysari injection solution or a composition of the catalpol injection solution and the radix astragali seu hedysari injection solution, the occurrence time of amyotrophic lateralizing sclerosis can be delayed, the survival time can be prolonged, and the limb movement function can be obviously improved. The catalpol and / or radix astragali seu hedysari extraction solution has the effects of resisting shrinkage of spinal anterior horn motor neuron cells, maintaining or activating the growth state of the spinal anterior horn motor neuron cells, resisting neuronal apoptosis and protecting the neurons, has an effect of gaining weight, and also has a high curative effect on the traumatic type nerve injury; meanwhile, the effective components of the catalpol and / or radix astragali seu hedysari extraction solution can be extracted from the traditional Chinese medicines; the used medicines are low-cost and easily available; the catalpol and / or radix astragali seu hedysari extraction solution has a good market prospect.

The invention relates to application of CART (Cocaine Amphetamine Regulated Transcript) in preparing medicaments for treating alzheimers diseases. In the invention, CART is prepared into injection preparations for treating alzheimers diseases, and the defects of the traditional medicaments for enhancing cholinergic action and N-methyl-D-aspartic acid (NMDA) receptor antagonists are overcome. The novel medicament has multiple target point actions on the generation and the degradation of A beta as well as the influence of the neurotoxicity and the molecular mechanism of the A beta. The invention has effects on effectively treating dementia with estrogen and up-regulating intracephalic CART; more CARTs are distributed in intracephalic hippocampus; CART exists in intracephalic acetylcholine neurons and can promote the release of acetylcholine; and mitochondrial dysfunction induced by A beta neurotoxicity is the main pathway for the A beta to cause neuronal apoptosis. The CART has a directaction on mitochondrial succinodehydrogenase subunit B and can maintain the respiration of mitochondria and the generation of energy, alleviate oxidative stress, stabilize mitochondrial membrane potential and prevent the mitochondria from being damaged, thereby inhibiting apoptosis.

A novel neuroprotectant was identified by microarray analysis that is differentially expressed between the ventricular zone and the cortex of human adult and fetal brain. The secreted protein antagonizes Wnt action in Xenopus embryos. Methods are described for modulating free radical neurotoxicity by contacting cells with the protein, treating neuronal diseases associated with free radical-mediated cell death by administering the protein, determining neuroprotective genomic targets associated with select free radical toxicity pathways by screening with the protein and using the protein to identify other compounds that modulate the biological activity of the secreted protein and the cell machinery that reacts to the secreted protein.

The invention discloses a preparation method of a directional EPC (endothelial progenitor cell) sample cell. The preparation method comprises the following steps: S1, collecting fat, and separating fat cells; S2, culturing the fat cells by virtue an ADSCs (adipose derived stem cells) culture medium to obtain a P2-generation ADSCs; and S3, culturing the P2-generation ADSCs by virtue of an EPCs (endothelial progenitor cells) culture medium to obtain a directional EPC sample cell. The directional EPC sample cell, the preparation method and the application have the beneficial effects adipose-derived stromal cells (ADSCs) are pre-induced for three days by adopting an endothelial progenitor cells culture medium to obtain heterogeneous CEL (committed EPC-like) with CD133 expression of 47.63+ / -12.50 percent and vWF expression of 31.10+ / -5.32 percent, and the CEL can increase the blood supply of an injured part, can alleviate ischemic symptom, and is not only beneficial for the structural restoration of an injured area, but also beneficial for alleviating the functional injury of a neurological function; and the CEL restores the blood supply by rebuilding a tissue structure of the injured area, thereby inhibiting the infection environment, reducing the neuronal apoptosis, promoting axonal regeneration and synaptic connection, and restoring partial feeling and movement function.

The invention provides shRNA for inhibiting expression of long-chain non-coding RNA MALAT1. The shRNA is designed for sites 286, 743, 1048 and 4807 of a MALAT1 transcript sequence NR_002847.3 in Genbank or corresponding sites in other transcript sequences. The invention further provides a corresponding plasmid, a lentivirus, a pharmaceutical composition and application of the pharmaceutical composition in treatment of cognitive impairment. The MALAT1-shRNA interference plasmid disclosed by the invention can be used for remarkably and specifically inhibiting the expression of MALAT1 in hippocampal neurons, promoting the process of a neuronal cell cycle and inhibiting neuronal apoptosis and the expression of apoptosis key proteins, so that the effect of resisting stress-induced neuronal cell injury is achieved.

The invention provides a nutritious food with brain-strengthening and intelligence-benefiting functions. The nutritious food with the brain-strengthening and intelligence-benefiting functions is prepared from phosphatidylserine, krill oil and sharpleaf galangal fruits. The krill oil is abundant in a plurality of unsaturated fatty acids, as well as rich in eicosapentaenoic acid (EPA), docosahexoenoic acid (DHA), phospholipids, flavonoids, VA, Ve, astaxanthin and the like; so that, the krill oil has obvious intelligence-benefiting and brain-strengthening effects. The phosphatidylserine is a member of the phospholipid family, and is the only phospholipid that can regulate functional status of key proteins in cell membranes. The sharpleaf galangal fruits are dried mature fruits of a perennialherb of the gingeraceae called sharpleaf galangal; and it has been found out by recent studies that the sharpleaf galangal fruits have significant neuroprotective effects, and are capable of significantly inhibiting neuronal apoptosis induced by glutamate excitotoxicity as well as significantly improving learning and memory abilities of rats with memory disorder caused by scopolamine and cerebralischemia. By matching the krill oil, the phosphatidylserine and the sharpleaf galangal fruits for eating, the nutritious food has more obvious brain-strengthening and intelligence-benefiting effects;and thus, the nutritious food is capable of significantly improving mental state, intelligence and memory of mental workers.

The invention discloses an application of a micromolecular polypeptide for inhibiting neuron apoptosis. According to the application, the micromolecular polypeptide with an amino acid sequence represented by SEQ ID No. 1 shown in the description is prepared through reforming and synthesizing a Glis2 structure; meanwhile, a rat model with intracerebral hemorrhage is modeled, the synthesized micromolecular polypeptide serves as a therapeutic drug for rat intracerebral hemorrhage, PBS serves as a blank control, the micromolecular polypeptide serves as a treatment group, shown by treatment on intracerebral hemorrhage, after being treated by the micromolecular polypeptide, the kinetism of the rat with intracerebral hemorrhage is recovered, the limb reflecting power is obviously increased, the quantity of macrophage activated and the expression level of inflammatory factors are obviously inhibited, and the quantity of nerve tissue cells subjected to apoptosis is reduced.

The invention discloses application of FTY720 to preparation of drugs used for inhibiting nerve cell apoptosis. FTY720 can inhibit inflammatory reactions, reduce cell apoptosis and alleviate secondarycerebral injury, thereby improving the prognosis of craniocerebral injury. Furthermore, results of injection of different doses of FTY720 into hippocampi of rats show that the proportion of apoptoticnerve cells, the activity of caspase-3 protein and the concentrations of interleukin-1beta, tumor necrosis factor-alpha and interleukin-6 in the hippocampi of a small-dose rat group, a middle-dose rat group and a large-dose rat group are significantly decreased compared with a model group, and are dose-dependent; thus, it is proved that a certain dose of FTY720 can effectively inhibit nerve cellapoptosis.