18 results about "Synaptic protein" patented technology

The disclosure relates to polynucleotides, e.g., viral genomes, encoding syntaxin-binding protein-1 (STXBP1), vectors, e.g., adeno-associated virus (AAV) particles, comprising said polynucleotides, compositions comprising said polynucleotides or vectors, and methods of making or delivering to a cell or subject. The polynucleotides, vectors, compositions, and methods of the present disclosure are useful for the treatment of subjects who have, have been diagnosed with having, or are at risk of having a STXBP1-related disorder, e.g., STXBP1 Developmental and Epileptic Encephalopathy (DEE) and / or other STXBP1-related disorders, or at least one symptom thereof.

The present invention relates to regions within the synaptogyrin-3 RNA sequence that are targetable by oligonucleotide inhibitors, such as antisense oligonucleotides. Specifically, these synaptogyrin-3 inhibitors are provided for general pharmaceutical use and for treating or inhibiting the progression of tauopathy or the symptoms of tauopathy.

The present application provides compositions and methods for targeting circular RNA, in particular to inhibit translation of circNlgn. Further provided is a single stranded, mixed base pair oligonucleotide ("mixmer") comprising a combination of ribonucleobases and deoxyribonucleobases, wherein the oligonucleotide comprises a sequence that is at least 80% complimentary with at least 10, at least 11, or from 11 to 15 consecutive nucleotides of the junction region of circular neuroligin RNA (circNlgn), and methods for using this mixmer as a medicine, for example, in the treatment of cardiac diseases or disorders, cancers, colitis or wounds.

The invention relates to the technical field of environmental endocrine disruptors, and discloses a biomarker for detecting EDC-induced glutamic acid synaptic dysfunction and a detection method thereof. The biomarker combination comprises molecules selected from at least one group of the following: presynaptic end function related proteins: plasma or cerebrospinal fluid (CSF) exosome levels including but not limited to synapsin-1 and vesicular glutamate transporter 1 (VGLUT1); proteins related to post-synaptic density and NMDA receptor functions include, but are not limited to, post-synaptic density protein 95 (PSD95), the phosphorylation level of a GluN1 subunit or soluble fragments thereof in CSF; the invention relates to astrocyte-neuron coupling related molecules. According to the invention, a multi-dimensional biomarker combination containing a presynaptic terminal function, a post-synaptic density and receptor function, astrocyte-neuron coupling and endoplasmic reticulum stress and calcium homeostasis is constructed, so that systemic evaluation of EDC-induced glutamic acid synaptic dysfunction is realized.

The present invention relates to a MuSK antibody-based molecule for use in the prevention or treatment of a disease or condition caused by a synaptinan deficiency in a human subject.

This invention discloses the application of AM80 agonists and the retinoic acid signaling pathway in the treatment of autism spectrum disorder, belonging to the field of pharmaceutical technology. This invention provides the use of AM80 or its pharmaceutically acceptable salts in the preparation of drugs for treating ASD. Experiments have demonstrated that AM80 can significantly improve social impairment and repetitive stereotyped behaviors in ASD model rats. Its mechanism of action is as follows: AM80, as a RARα agonist, can upregulate the activity of the RA / RARα signaling pathway, thereby promoting the transcription and expression of the downstream target molecule TREM2. Elevated TREM2 can correct the abnormal activation of microglia (reducing their number, improving their morphology, and promoting their conversion from pro-inflammatory M1 to anti-inflammatory M2) and improve synaptic pruning function (regulating the expression of synaptic proteins such as SYN-1, PSD95, and Gephyrin). This invention provides new drug candidates and targets for the treatment of ASD.

Disclosed herein are compounds that disrupt the protein-protein interaction between Muncl3-4 and syntaxin 7, methods of discovering such compounds, and methods of their use to treat systemic inflammation.

Methods for enhancing transcytosis comprising modulating expression of Vesicle-associated membrane protein 3 (VAMP3) and syntaxin 4 (STX-4). Composition for increasing expression of VAMP3 and / or STX-4 in HBMECs and compositions comprising target molecules in a form suitable for transcytosis across the blood brain barrier.

Described are RNAi agents, compositions that include RNAi agents, and methods for inhibition of a synuclein alpha (SNCA) gene. The SNCA RNAi agents and RNAi agent conjugates disclosed herein inhibit the expression of an SNCA gene. The SNCA RNAi agents are conjugated to an antigen binding protein that may enable subcutaneous delivery of the RNAi agents by facilitating crossing of the blood brain barrier (BBB). Pharmaceutical compositions that include one or more SNCA RNAi agents, optionally with one or more additional therapeutics, are also described. Delivery of the described SNCA RNAi agents to central nervous system (CNS) tissue, in vivo, provides for inhibition of SNCA gene expression and a reduction in SNCA activity, which can provide a therapeutic benefit to subjects, including human subjects, for the treatment of various diseases including Parkinson's Disease.

The present disclosure relates to an application of a peptide in preparing drugs for treating and / or preventing cognitive impairment, belonging to the technical field of drugs for cognitive impairment. The present disclosure discloses an application of an artificially synthesized small molecule peptide in preparing drugs for treating and / or preventing cognitive impairment. When the peptide in the present disclosure is applied to cognitive impairment models, it may effectively play its biological role in blocking the binding between Synapsin IIb (Syn2b) and AMPA receptor subunit (GluA2), enabling the increase of GluA2 membrane expression, increase of AMPA current, enhancement of neuronal excitability and synaptic transmission, thereby alleviating learning and memory impairment in cognitive impairment model mice to some extent.

Disclosed herein are methods for diagnosing a subject as having a neurological disorder, such as Alzheimer's disease, using proximity-based detection assays capable of detecting complexes containing two or more synaptic proteins, such as neuronal pentraxins, from a blood, cerebrospinal fluid, or other fluid sample of the subject. Also disclosed are methods of evaluating and monitoring subjects having or at risk of developing a neurological disorder using the aforementioned assays.

Provided herein are methods and compositions for identifying α-synuclein aggregation inhibitors. Also provided are methods of use of the α-synuclein aggregation inhibitors; the methods include methods of inhibition the formation of Lewi bodies and methods of treating synucleinopathies in subjects. Methods are compositions provided herein include optogenetic α-synuclein fusion proteins and an optogenetic alpha-synuclein (α-syn) aggregation system. Further, provided herein are compositions comprising α-synuclein aggregation inhibitor drug candidates identified using an optical alpha-synuclein aggregation screening system. The α-synuclein aggregation inhibitor drug candidates have neuroprotective effects in vitro and in vivo and provide proof-of principle that the optical alpha-synuclein aggregation screening system can be used to identify drug candidate for synucleopathies and tauopathies, including for example Parkinson's disease.

The present invention describes compounds of formula (A) for use as Parkinson's disease modifying-agents, said formula (A). Surprisingly it has been found that the compounds of the invention can significantly reduce alpha-synuclein aggregation and stimulate the functional interaction between al-pha-synuclein and Synapsin III.

The lithium salt according to one aspect triggers a mechanism that exhibits long-lasting therapeutic effects on various signaling pathways and synaptic proteins during early treatment of autism spectrum disorder, and has the effect of improving excitatory synaptic density, microcephalus, or brain development / function. Accordingly, the lithium salt can be advantageously used for the treatment of autism spectrum disorder, particularly autism spectrum disorder associated with DYRK1A mutation.

The disclosure relates to adeno-associated (AAV) particles comprising viral genomes encoding syntaxin-binding protein-1 (STXBP1), compositions comprising said AAV particles, and methods for making or delivering said AAV particles to a cell or subject. The AAV particles, compositions, and methods of the present disclosure are useful for the treatment of subjects who have, have been diagnosed with having, or are at risk of having a STXBP1-related disorder, e.g., STXBP1 Developmental and Epileptic Encephalopathy (DEE) and / or other STXBP1-related disorders, or at least one symptom thereof.

The invention relates to application of polyphyllin II in preparation of a medicine for relieving learning and memory impairment induced by diethyl hexyl phthalate (DEHP). Aiming at neurotoxicity and cognitive defects caused by DEHP exposure, the invention reveals that the polyphyllin II plays roles through dual mechanisms: inhibiting release of inflammatory factors such as TNF-alpha, IL-6 and the like, down-regulating expression of TNFAIP1, activating a CREB signal channel and recovering protein levels of BDNF and Bcl-2; miR-93 expression is up-regulated, TNFAIP1 is inhibited in a targeted manner, and DEHP-induced synaptic plasticity injury is blocked. According to the technical scheme, polyphyllin II and DEHP are combined for use, and behavioristics and histology verify that the learning and memory ability of mice is remarkably improved (the incubation period is shortened, and the target quadrant residence time is recovered by 40% or above), neuron loss is reversed, and synaptic protein down-regulation is performed (the synaptic protein is recovered to a healthy group by 85% or above, plt, 0.01).

The application discloses a method for producing recombinant human proteins in industrial microorganisms, comprising the following steps: introducing a gene coding alpha synuclein into corynebacterium glutamicum by genetic engineering technology to realize expression of the alpha synuclein; and isolating the alpha synuclein in liquid droplet-like membraneless organelles by liquid-liquid phase separation technology to further improve protein yield. Compared with the most widely used Escherichia coli expression system, the method has the following advantages: the method uses corynebacterium glutamicum as a new type of chassis cell, and overcomes problems such as endotoxin pollution and insoluble inclusion body formation in a traditional Escherichia coli expression system; the method significantly improves the yield of alpha synuclein by applying liquid-liquid phase separation technology; the method is not only suitable for the production of alpha synuclein, but also can be popularized to other difficult-to-express proteins, and provides a new technical path for the field of biological pharmacy.