33 results about "Synaptic protein" patented technology

Provided is a polypeptide which contains a polypeptide having at least 80%, 85%, 90%, 95%, or 99% identity to amino acid sequence MTYRPGYNPFG (SEQ ID NO: 41) or amino acid sequence AKGYYRPYGVPV (SEQ ID NO: 22), or a polypeptide having one or more amino acid substitutions, deletions and / or additions relative to the amino acid sequence as shown in SEQ ID NO: 41 or 22. The provided polypeptide can interfere with the binding of a Brag2 synaptic protein to the C terminus of an AMPA receptor, thereby inhibiting NMDA-mediated excessive endocytosis of an AMPA receptor and neuronal apoptosis, and playing a role in protecting neuronal cell activity. Therefore, the polypeptide has application prospects and potential development values as a drug for treating nervous system diseases such as strokes, depression, Alzheimer's disease and drug addiction.

Disclosed herein are multifunctional polypeptides comprising an optional signal peptide sequence, a cell penetrating peptide, an antigen binding domain (e.g., anti-synuclein, anti-tau, anti-huntingtin), and a programmable proteasome-targeting PEST motif, and methods for using these polypeptides in treatment of protein aggregation diseases, e.g., neurodegenerative diseases.

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 addresses the problem of providing an antibody excellent in binding to an intravesicular domain of synaptogyrin 3.　Provided is a synaptogyrin 3 antibody capable of efficiently targeting a desired substance toward a motor neuron synapse.

The present disclosure relates to engineered depalmitoylases. S-Palmitoylation is a reversible post-translational modification that tunes the localization, stability, and function of an impressive array of proteins including ion channels, G-proteins, and synaptic proteins. Altered protein palmitoylation is linked to various human diseases including cancers, neurodevelopmental and neurodegenerative diseases. Disclosed herein is an engineered chemogenetic depalmitoylase that manipulates the palmitoylation status of target proteins using a chemically inducible dimerization system. In some aspects, the engineered chemogenetic depalmitoylase is programed to allow selective depalmitoylation in specific organelles, of individual protein complexes, or triggered by cell-signaling events. Also disclosed is an engineered depalmitoylase that allows depalmitoylation of proteins in response to Erk phosphorylation. An optogenetic actuator to manipulate protein palmitoylation is also disclosed. The disclosed engineered depalmitoylases represent versatile and powerful methods for manipulating protein palmitoylation in live cells.

The present invention relates to the field of vectors, in particular to recombinant viral vectors suitable for in vivo delivery of therapeutic genes. Described is an adeno-associated virus (AAV) vector comprising (i) a human growth hormone intron 3 (hGHi3) sequence, (ii) a synaptic promoter sequence and / or (iii) a granulin precursor 3'untranslated region (UTR) sequence operatively linked to a polynucleotide sequence encoding a polypeptide of interest. Particular uses of such vectors are to enhance the expression of a polypeptide of interest, such as a granulin precursor (PGRN), to treat subjects having gene mutations or intrinsic polypeptide levels below physiologically normal levels.

The present invention addresses the problem of providing an antibody that excels at binding to the intravesicular domain of synaptophysin.　Provided is a synaptophysin antibody capable of efficiently targeting a desired substance toward motor neuron synapses.

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.

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 invention relates to the field of biomedicine, and in particular to the use of neurogenic exosomal synaptophysin in the preparation of a product for treating non-dementia obstructive sleep apnea. By detecting the expression level of the biomarker neurogenic exosomal synaptophysin in a sample, it is possible to diagnose whether a subject has non-dementia obstructive sleep apnea, enabling early intervention and effective treatment.

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 field of biological medicines, in particular to a polypeptide, which comprises a polypeptide having at least 80%, 85%, 90%, 95% or 99% identity with an amino acid sequence MTYRPGYNPFG (SEQ ID NO: 41) or an amino acid sequence AKGYYRPYGVPV (SEQ ID NO: 22), or a polypeptide having one or more amino acid substitution, deletion and / or addition with the amino acid sequence shown as SEQ ID NO: 41 or 22. The polypeptide provided by the invention can be used for inhibiting NMDA-mediated AMPA receptor excessive endocytosis and neuronal apoptosis by interfering the mutual combination of the C terminal of the AMPA receptor and a Bragg 2 synaptic protein, so that the effect of protecting the activity of neuronal cells is achieved; therefore, the compound has an application prospect and a potential development value as a medicine for treating nervous system diseases such as cerebral apoplexy, depression, Alzheimer's disease, drug addiction and the like.

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.

The present invention addresses the problem of providing an excellent antibody that binds to an intravesicular domain of synaptophysin.　Provided is a synaptophysin antibody with which a desired substance can efficiently target a motor neuron synapse.

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.

The present invention addresses the problem of providing an antibody that excels at binding to the intravesicular domain of synaptophysin.　Provided is a synaptophysin antibody with which it is possible to efficiently target a desired substance toward motor neuron synapses.

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 invention addresses the problem of providing an antibody excellent in binding to an intravesicular domain of synaptophysin.　Provided is a synaptophysin antibody capable of efficiently targeting a desired substance toward a motor neuron synapse.

The present disclosure describes antisense oligonucleotides (ASOs) that target regions in a STXBP1 pre-mRNA. In certain embodiments, the ASOs are splice switching oligomers (SSOs) which target specific pre-mRNA splicing regulatory elements encoded in the STXBP1 gene and modify STXBP1 pre-mRNA splicing through steric blocking of the targeted splicing regulatory element. The present disclosure also describes methods for modifying the expression of Syntaxin binding protein 1 (STXBP1) using ASOs of the present disclosure. The present disclosure also describes methods of treating STXBP1 -related diseases, including developmental epileptic encephalopathy (DEE), by restoring canonical STXBP1 splicing and upregulating STXBP1 mRNA production using ASOs of the present disclosure.

The invention relates to a kit for detecting alpha-synapsin oligomer and application of the kit, and belongs to the technical field of protein detection. Wherein a combination pad of the lateral flow test paper contains gold nanoparticles coupled with a first split aptamer and first DNA for quality control, and a detection line of the lateral flow test paper is loaded with a biotinylated second split aptamer combined with streptavidin; a biotinylation second quality control DNA combined with streptavidin is loaded on a quality control line of the lateral flow test paper; the base sequence of the first split aptamer is as shown in SEQ ID No. 1, and the base sequence of the second split aptamer is as shown in SEQ ID No. 2; the first DNA for quality control and the second DNA for quality control comprise complementary base sequences. According to the invention, the simple, portable, economical and efficient lateral chromatography test paper is established by utilizing the characteristic of the split aptamer (two chains can form a correct secondary structure through hybridization and develop color only in the presence of a target), and early diagnosis and visual analysis of a PD patient are realized.

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.