The present invention relates to bispecific antibodies that bind to transferrin receptor and BACE1 and methods of using the same.

The present disclosure provides, among other things, methods for using presenilin based gene therapy to treat neurodegenerative dementia including, but not limited to Alzheimers disease, frontotemporal dementia, frontotemporal lobar degeneration, Picks disease, Lewy body dementia, memory loss, and cognitive impairment including mild cognitive impairment (MCI).

The invention provides antagonistic antibodies to BACE1 and methods of using the same for the treatment of neurological disease and disorders.

Provided herein are formulations effective for and methods of treating or preventing a neurodegenerative disorder in a subject in need thereof that can include administering an amount of an aPKC inhibitor to a subject in need thereof.

Provided herein are formulations effective for and methods of treating or preventing a neurodegenerative disorder in a subject in need thereof that can include administering an amount of an aPKC inhibitor to a subject in need thereof.

Described herein are methods, systems and compositions for the treatment of neurodegenerative diseases and disorders. In various embodiments neurotrophins, such as Pituitary Adenylate Cyclase Activating Polypeptide (PACAP) can be used for the treatment methodologies contained herein. In one embodiment, a method of treatment of Alzheimer's Disease by administering a composition comprising PACAP.

Provided herein are formulations effective for and methods of treating or preventing a neurodegenerative disorder in a subject in need thereof that can include administering an amount of an aPKC inhibitor to a subject in need thereof.

The present invention relates to the design and development of recombinant protein for the delivery of silencer RNA complex to mediate RNA interference since it represents a novel therapeutic approach to modulate several neurodegenerative disease-related genes across the blood-brain barrier (BBB). To overcome challenges due to this barrier for biologics and other biological complex, the present invention describes a method wherein peptide having sequence GGGGHLNILSTLWKYRC represented by SEQ ID NO. 1 known to target specific gangliosides was linked to a double-stranded RNA binding protein to bind and deliver silencer RNA to the brain parenchyma. The designed fusion protein comprising a double-stranded RNA-binding domain (dsRBD) of human Trans Activation response element (TAR) RNA Binding Protein (TARBP2) and a brain targeting peptide sequence that binds GM1. Conformation-specific binding of TARBP2 domain to silencer RNA results in the formation of homogenous serum-stable complex with GM1 targeting potential. Uptake of the complex in neural cells reveals selective requirement of GM1 for entry. Remarkably, the invention pertains to the systemic delivery of the complex comprising TARBP-BTP and silencer RNA in APP-PS1 mouse model of Alzheimer's disease (AD) led to distinctive localization primarily in the cerebral hemisphere in the hippocampus and brain cortex and in principle can work across other mammalian CNS targets. Further, the delivery of silencer-RNA mediated by brain targeting peptide fusion led to significant knockdown of BACE1, a therapeutic protease target in both APP-PS1 and wild type C57BL/6 mice. The invention establishes the emergent importance of fusion proteins in delivering therapeutic siRNA as a simple complex to brain tissues to treat neurodegenerative diseases besides Alzheimer's disease (AD). The complex is also useful to study gene function of hitherto unidentified genes/interplay of genes in mammalian systems and central nervous system.

In order to provide a membrane protein production method which does not require the step of solubilizing a membrane protein and which allows the membrane protein having an excellent quality to be obtained with a high yield, a method in accordance with an embodiment of the present invention includes: a step (a) of preparing a reaction solution for cell-free protein synthesis, the reaction solution containing (i) a template nucleic acid which encodes the membrane protein, (ii) a lipid, and (iii) a detergent which is contained at a concentration equal to or higher than a critical micelle concentration; and a step (b) of synthesizing the membrane protein while the concentration of the detergent in the reaction solution is maintained at a concentration equal to or higher than a critical micelle concentration.

The present disclosure discloses preparation and use of sugar-targeting nanoparticles for modifying siRNA. A sugar-targeting nanoparticle, including targeting nanocarriers, wherein the targeting nanocarriers are formed by linking in sequence a targeting molecule, a first linking compound, a first hydrophilic biomaterial, a second linking compound and a cationic compound through chemical bonds; the first linking compound and the second linking compound both have a carboxyl group; the first linking compound has a maleimido group at the same time, and the targeting molecule is a cycloaldohexose. Providing the cycloaldohexose as the targeting molecule facilitates the nanoparticles targeting the GLUT-1 protein on the capillary endothelial cell membrane on the blood brain barrier, and the nanoparticles are transferred to the brain with high efficiency through the effect of the GLUT-1 protein to transport cycloaldohexose, thereby effectively penetrating the blood brain barrier, and helping to improve the efficiency of sugar-targeting nanoparticles penetrating the BBB.