This document relates to materials and methods for controlling ligand gated ion channel (LGIC) activity. For example, modified LGICs including at least one LGIC subunit having a modified ligand binding domain (LBD) and/or a modified ion pore domain (IPD) are provided. Also provided are exogenous LGIC ligands that can bind to and activate the modified LGIC, as well as methods of modulating ion transport across the membrane of a cell of a mammal, methods of modulating the excitability of a cell in a mammal, and methods of treating a mammal having a channelopathy.

The present invention relates to a sorLA-based drug screening platform for use in screening compound libraries for an effect on endosomal activity.

Disclosed herein are designer extracellular vesicles (EVs) functionalized with glutamate receptors (e.g., mGluR4 and mGluR8), which can selectively target injured regions of the CNS experiencing excitotoxicity. mGluR4 and mGluR8-decorated EVs preferentially anchor into injured areas of the CNS with a marked increase in extracellular glutamate associated with profuse neuroand excitotoxicity. Therefore, glutamate receptor decoration can lead to enhanced homing in glutamate-rich areas of the CNS.

There is provided in the present application a pharmaceutical composition comprising a peptide comprising the amino acid sequence of YEKLLDTEI (SEQ ID NO: 1) or a functional variant thereof, a pH adjusting agent, and a filler. The peptide is an active peptide for the treatment of a central nervous system injury. The present application also provides a pharmaceutical composition comprising a chimeric peptide comprising an active peptide and an internalization peptide, a pH adjusting agent, and a filler. The present application also provides medical use of a pharmaceutical composition comprising the active peptide or the chimeric peptide.

The present invention relates to mutant transmembrane proteins which have increased conformational stability when compared to their parent protein, methods of selection and production. In particular the invention relates to mutant transmembrane proteins which are mutated in or in the proximity of the transmembrane alpha helices or in a kinked region or in an alpha-helix adjacent to a kink. The mutant transmembrane proteins have use in crystallisation studies and also in screening to identify compounds for use in drug discovery and therapy.

Provided herein are generalized extracellular molecule sensors (GEMSs) and polynucleotides encoding the GEMSs. Also provided herein are methods of making and using the GEMSs, such as therapeutic and diagnostic methods.

The present invention discloses an application of a β3 adrenergic receptor (ADRB3) as a marker for detecting a plurality of diseases, and an application of anti-human ADRB3 monoclonal antibody in diagnosing a disease and preparing a drug for treating the disease. The present invention finds through research that the ADRB3 is a key receptor in nerve-endocrine-immunoregulatory network, and an ADRB3-mediated signaling pathway regulates proliferation and differentiation of neutrophils, lymphocytes and tumor cells. Under normal circumstances, the ADRB3 maintains the non-specific immunocompetence and specific immunocompetence of an organism, and eliminates pathogenic microorganisms and aged organism tissues to play a role in protecting the organism and anti-aging. Under pathological conditions, excessive activation of the signaling pathway will cause systemic chronic inflammation, and destroy immune homeostasis. Therefore, the ADRB3 can be used as a diagnostic marker and a therapeutic target for a plurality of diseases. Anti-human ADRB3 antibody can specifically bond with the ADRB3, regulate the activity of the ADRB3, has the functions of resisting cancer, inflammation, poisoning, shock, allergy, viral infection, autoimmune disease, disease caused by regenerative dysfunction, autoimmune disease, cachexia, cardiovascular and cerebrovascular disease, neurodegenerative disease and aging, regulating autophagy, treating aging disease, etc., and has important medical value and research and application prospects.

The serotonin receptor 5HT2A (5HT2aR) and membrane NADPH oxidases (NOX enzymes) are found to be a target of autoantibodies present in Multiple Sclerosis patients. The present invention refers to peptides comprised in the extracellular regions of the human 5HT2aR and/or NOXs for diagnosis and therapy of Multiple Sclerosis.

The invention provides variants of a previously described active agent for treating stroke, Tat-NR2B9c, in which target binding characteristics are retained by inclusion of L-amino acids at the C-terminus and plasmin-resistance is conferred by inclusion of D-amino acids elsewhere. An exemplary agent has the sequence ygrkkrrqrrrklssIETDV (SEQ ID NO:62). The resulting active agents have several advantages including administration at the same time as thrombolytic agents without significant loss of activity due to plasmin digestion. The resulting agents are also more suitable for administration by alternative routes to intravenous infusion, such as subcutaneous, intranasal and intramuscular, and for multi-dosing regimes for treatment of chronic conditions.

The invention provides nucleic acids and nucleic acid expression vectors containing optimized mGluR6 promoters for expression of transgenes in the retina. The compositions and methods of the invention are useful for expression of gene products to preserve, improve, or restore phototransduction or vision.