17 results about "Neuron survival" patented technology

This invention relates to diselenylene-bridged mesoporous silica nanoparticles loaded with baicalin and their applications. The invention constructs a ROS-responsive, microglia-inspired Ba@Se-MSN&BV2 nanoplatform targeting the secondary phase of spinal cord injury. The BV2 cell membrane-mediated enrichment at the injury site, combined with the diselenylene-triggered, on-demand release of baicalin, enables targeted intervention in a highly oxidative and pro-inflammatory microenvironment. In vitro and in vivo studies show that Ba@Se-MSN&BV2 can alleviate oxidative stress and mitochondrial dysfunction, inhibit apoptosis, promote axonal and neuronal survival, and improve motor circuit function. This invention provides a new therapeutic target and research direction for neuroinflammatory injuries driven by redox homeostasis disruption, with significant clinical application prospects and social value.

Provided are methods of treating spinal muscular atrophy (SMA) using a combination of a 15-hydroxyprostaglandin dehydrogenase (15-PGDH) inhibitor and an agent that increases motor neuron survival (SMN) protein expression. Furthermore, provided herein is a composition, a pharmaceutical formulation, or a kit comprising a 15-hydroxyprostaglandin dehydrogenase (15-PGDH) inhibitor and an agent that increases the expression of a motor neuron survival (SMN) protein.

The present invention provides novel irisin peptides (e.g, irisin glycosylation mutants and biologically active fragments thereof). Also provided are methods for preventing or reducing degeneration of dopaminergic neurons and / or preventing or ameliorating at least one motor deficit in a subject in need thereof, such as in a subject with α-synucleinopathy, using the novel irisin peptides to modulate irisin-induced integrin signaling. The novel irisin peptides can also be used in methods for increasing expression of brain-derived neurotrophic factor (BDNF), and / or treating or preventing neurological diseases or disorders that would benefit from decreased neuronal cell death and / or increased neuronal survival in a subject. In addition, the novel irisin peptides may be used in methods for preventing or treating muscular atrophy or muscular dystrophy.

The present application relates to the technical field of biological medicine, and particularly relates to a composition for protecting cochlear spiral ganglion neurons and application thereof. The composition comprises Panax notoginseng saponins (PNS) and Polygonatum sibiricum polysaccharide (PSP). Research shows that the composition can significantly improve the survival rate of neurons, promote neurite growth, reduce the level of reactive oxygen species, inhibit cell apoptosis, and promote autophagy by regulating the PI3K / AKT signaling pathway, thereby effectively resisting ototoxicity damage induced by aminoglycoside antibiotics. The present application further provides the use of the composition in the preparation of a drug for preventing or treating sensorineural hearing loss.

Disclosed is a method of determining whether a human subject is not a carrier of spinal muscular atrophy (SMA). This method includes the steps of (i) collecting a genomic deoxyribonucleic acid (DNA) sample from a human subject; (ii) screening the genomic DNA sample to determine the human subject's copy number of survival of motor neuron 1 (SMN1) gene and whether one of the copies of the SMN1 gene is positive for a polymorphism associated with non-carriers of SMA having two copies of the SMN1 gene; and (iii) determining the human subject as not a carrier of SMA if the human subject includes two copies of the SMN1 gene with one of those copies being positive for the polymorphism. Also disclosed is a method of determining whether an individual has a decreased risk of being a carrier of spinal muscular atrophy (SMA), where the individual is identified to have a decreased risk of being a carrier of SMA when the individual has two copies of the SMN1 gene with one of those copies being positive for the polymorphism.

To provide a combination therapy for spinal muscular atrophy.SOLUTION: Aspects of the present application relate to compositions and methods for treating spinal muscular atrophy in a subject. In particular, this application provides therapeutically combinations of recombinant nucleic acids encoding Survival of Motor Neuron 1 (SMN1) proteins (e.g., in viral vectors) and antisense oligonucleotides (ASOs) that increase full-length Survival of Motor Neuron 2 (SMN2) mRNA (e.g., ASOs that target nucleic acids molecules encoding Survival of Motor Neuron 2 (SMN2) and promote inclusion of exon 7 in SMN2mRNA).SELECTED DRAWING: None

The invention discloses a small molecule activator targeting nerve cell aromatase and application of the small molecule activator in cerebral ischemia injury, and belongs to the technical field of biological medicine. The activator can directly enhance the catalytic activity of aromatase without significantly affecting the gene transcription of aromatase, so that the local estrogen level in the brain is accurately improved, and the neuroprotection effect is achieved. The neuron aromatase is specifically activated, so that the side effect of systemic estrogen treatment is avoided. In-vivo and in-vitro experiments prove that the concentration of estrogen in a target region can be effectively improved through local intracerebral administration, and the survival rate of neurons in an oxygen-glucose deprivation / reoxygenation injury model is remarkably improved. The pharmaceutical composition provided by the invention is suitable for local administration or systemic administration of a central nervous system, can be combined with the existing therapy, and provides a brand new treatment strategy and drug candidate for cerebral ischemia injury.

Disclosed herein include systems, devices, computer readable media, and methods for paralog geno typing, such as determining a copy number of survival of motor neuron 1 gene and genotyping cytochrome P450 family 2 subfamily D member 6 gene using a Gaussian mixture model comprising a plurality of Gaussians each representing a different integer copy number.

The invention relates to a compound of formula (I), for use in treating GM1 gangliosidosis. Specifically, the invention relates to a compound of formula (I) for use in reducing the accumulation of GM1 ganglioside in the brain and / or spinal cord of a subject, increasing neuronal survival in a subject, and / or preventing neuronal degeneration in a subject.

The application discloses a kind of by application specific deacetylase activator Targeted elimination mitochondrial apoptosis-inducing factor (AIF) lysine (K295) position 295 Acetylation modification, effectively inhibit ischemic stress under AIF from mitochondria to the abnormal translocation of nucleus, block its mediated chromosomal DNA fragmentation process, and then significantly reduce the level of neuronal programmed death, thereby reduce the brain injury after stroke.In cell and mouse stroke model, after the specific elimination of AIF K295 acetylation modification, the survival rate of neurons is increased by 4 times (p<0.01), and the cerebral infarction volume is reduced by 40% (p<0.01).The application provides a new drug action target and treatment strategy for the development of neuroprotective therapy after stroke.

The invention relates to the field of neuroscience experiments, and discloses a method for increasing the survival rate of brain slice neurons through intrathecal injection of KN93, which comprises the following steps: intrathecal injection: carrying out intrathecal injection of an injection containing KN93 into an experimental animal, the concentration of KN93 in the injection being 5-20 [mu] M; preparing a brain slice: after injection is completed, anesthetizing the experimental animal, cutting the head, taking the brain, cooling the brain tissue, and cutting to form the brain slice; incubating the brain slice: incubating the brain slice in artificial cerebrospinal fluid; and survival rate evaluation: evaluating the neuron survival rate of the brain slice at a preset time point. KN93 directly enters cerebrospinal fluid circulation through intrathecal injection to target calcium / calmodulin dependent protein kinase II in central neurons and block excessive activation of the protein kinase II, so that neuronal death in the brain slice preparation and incubation process is reduced, the survival rate and functional integrity of neurons after long-time incubation are improved, and the brain slice has a good application prospect. And the survival time of brain slice neurons is effectively prolonged.

The present application relates to the fields of genetics, gene therapy, and molecular biology. More specifically, the present invention relates to an isolated codon-optimized nucleic acid that encodes the SMN1 protein (survival motor neuron protein), an expression cassette and a vector based thereon, as well as an AAV9 (adeno-associated virus serotype 9)-based recombinant virus for increasing the expression of the SMN1 gene in target cells, and use thereof.

Provided herein are peptide amphiphiles (PAs) and supramolecular PA nanostructures that mimic glial derived neurotrophic factor (GDNF), a growth factor that induces neuronal survival, maturation, and increased electrical activity. In particular, injectable biomaterials comprising GDNF mimetic PAs are provided, as well as methods of using GDNF mimetic PAs for the treatment or prevention of neurological injuries, diseases, and disorders, including concurrently with cell replacement therapy.

The invention discloses a construction method of a microglial cell and neuronal cell co-culture model. The construction method comprises the following steps: performing non-contact co-culture on microglial cells and neuronal cells, and then adding IL-33 for induction to obtain the co-culture model. According to the construction method disclosed by the invention, the microglial cells and the neuronal cells which are co-cultured in a non-contact manner are induced through IL-33, so that bidirectional signal transmission between the microglial cells and neurons can be captured, and the bidirectional signal transmission comprises a supporting effect of the microglial cells on neuronal survival and synaptic formation through neurotrophic factors; and a regulation mechanism of neurons on immunocompetence of the microglial cells lays a foundation for researching a molecular regulation network of signal transmission between the microglial cells and the neuronal cells. Besides, the method can also be used for screening candidate drugs having influence on neuron-microglial cell interaction, and a reliable in-vitro evaluation tool is provided for research and development of the candidate drugs and screening of functional probiotics and prebiotics, so that the method has a wide application prospect.

The invention provides engineered mesenchymal stromal cells (ePSCs) with a phagocytosis function and an application of the engineered mesenchymal stromal cells (ePSCs) in treatment of Alzheimer's disease (AD). The engineered mesenchymal stromal cells (ePSCs) are obtained by inducing fibroblasts to be reprogrammed by adopting a chemical small molecule combination. The invention discloses a set of genetic modification-free reprogramming scheme based on a chemical small molecule composition, which is used for efficiently converting fibroblasts from somatic cells into ePSCs (enhanced pluripotent stem cells) by sequentially activating an endogenous reprogramming pathway. The obtained ePSCs highly express phagocytic function related proteins (including TMEM119, SCARB1, APOE, CTSD and the like), and the ability of removing beta amyloid protein (A beta) plaques is significantly enhanced. In-vitro and in-vivo AD model verification proves that transplanted ePSCs can be directionally migrated to an intracerebral lesion area, and through a synergistic effect mechanism: (i) directly phagocytizing and degrading A beta aggregates, and (ii) providing neuroprotective factors (such as HTRA1, GLUL, SLIT1, TUBB3 and NPTX2) to inhibit neuroinflammatory response, promote nerve regeneration, effectively improve the neuron survival state and synaptic function integrity, and improve the neurological activity of the brain. And finally, cognitive function recovery is promoted.

The invention relates to the technical field of nerve interfaces, in particular to a biological mixed nerve interface. According to the technical scheme, the device comprises a three-dimensional multi-layer structure electrode, composite conductive hydrogel, a neuron layer and a signal decoding module, the three-dimensional multi-layer structure electrode comprises a three-dimensional cavity multichannel electrode layer, the three-dimensional cavity multichannel electrode layer is provided with a plurality of independent micro cavities, and each micro cavity loads the composite conductive hydrogel and the neurons in an adaptive mode. According to the biological mixed nerve interface, through the three-dimensional cavity multi-channel design of the three-dimensional multi-layer structure electrode, the supporting regulation and control of the methacrylamide esterified gelatin hydrogel and the nerve cell axon extension characteristic, high-precision electric signal collection and single-nerve-cell-level precise electrical stimulation are achieved, nerve cell survival and regulation and control are guaranteed, and the biological mixed nerve interface has the advantages of being simple in structure, convenient to operate and high in reliability. The action potential of neurons in the cortex can be collected only by implanting into the brain surface so as to record high-quality electroencephalogram signals, and meanwhile nerve tissue trauma is reduced and biocompatibility is improved.

The invention discloses application of sesquiterpene variecolactone in preparation of a medicine for treating Alzheimer's disease, and belongs to the field of biological medicine. As a PDE4 inhibitor, the sesquiterpene variecolactone provided by the invention can be used for treating the Alzheimer's disease, and no obvious side effect is found. Experiments prove that the sesquiterpene variecolactone can activate a cAMP-PKA-CREB pathway in SY5Y-APP cells by inhibiting PDE4 (phosphodiesterase 4), so that the effects of improving the survival of neurons, eliminating A beta and recovering the morphology of damaged mitochondria are achieved; therefore, the purpose of treating the Alzheimer's disease is achieved.