Abstract: Disclosed herein are materials and methods for the treatment of stress-related disorders and cancer. The disclosure provides an antibody, or antigen binding fragment thereof, that specifically binds to a region of corticotropin-releasing hormone (CRH). The disclosure also provides methods of treating a disorder associated with HPA axis activation, such as a stress-related disorder or cancer, comprising administering to a subject in need thereof an antibody or antigen binding fragment thereof described herein in an amount effective to treat the disorder.

Abstract: Provided herein are chimeric receptors, engineered cells and pharmaceutical compositions for enhancement of long-term clearance of protein aggregates in the central nervous system via phagocytosis or engulfment. Further provided herein are methods of treatment of subjects suffering from, or diagnosed with, a neurodegenerative disease by administering these receptors, modified cells, and/or pharmaceutical compositions. Administration of one or more, or a plurality of these modified cells, to a subject may provide treatment of a neurodegenerative disease such as Alzheimer's Disease (AD) or Parkinson's Disease (PD). Advantageously, the modified cells, pharmaceutical compositions, and methods of the present disclosure meet existing needs in the art by providing clearance of accumulations of protein aggregates in brain tissue in PD and AD pathologies.

Abstract: Disclosed herein are monoclonal antibodies targeting specific tau epitopes, particularly, microtubule binding domain region 2 or region 4. Also disclosed herein are antibodies or antigen binding fragments thereof that specifically recognize a tau epitope consisting of the amino acid sequence of SEQ ID NO: 9 or 11. Also disclosed herein are methods of detecting tau protein in a subject, comprising performing an assay using the antibodies or antigen binding fragments thereof on the subject or on a biological sample obtained from the subject. Assay kits containing the disclosed antibodies are also provided. Further, methods of treating or preventing a tauopathy in a subject by administering to the subject tau antibodies or antigen-binding fragments thereof are provided.

Abstract: Provided herein are compositions and methods for the stable production of bioactive small peptides of interest through delivery to target cells based on the fusion of small peptides of interest to a collagen domain of a C1qTNF protein to produce a novel scaffold protein capable of multimerization. Advantageously, the fusion proteins, compositions and methods of the present disclosure meet existing needs in the art by providing for higher stable expression and longer stability of intracellular and secretable peptides of interest. Additionally, the fusion proteins, compositions and methods of the present disclosure provide for improved binding affinity of expressed receptor peptides with ligand binding partners in the target cell. Further provided herein are polynucleotide constructs encoding the described fusion proteins and recombinant adeno-associated viral particles comprising these polynucleotides.

Abstract: Provided herein are improved, cost-effective and environmentally friendly methods of production of recombinant AAV (rAAV) in embryonated avian eggs. Further provided herein is a provides embryonated avian eggs as novel host vehicles for high-yield production of rAAV, including both packaging and propagation. In particular, embryonated chicken eggs provide a novel expression vehicle for AAV of mammalian origin, irrespective of AAV serotype. The disclosed methods may comprise packaging of rAAV in embryonated avian eggs (e.g., chicken eggs) by inoculating an embryonated avian egg with a first nucleic acid vector comprising a transgene and a second nucleic acid vector comprising AAV rep and cap genes, incubating the egg, and isolating rAAV from the egg, wherein the AAV is of non-avian origin. Also provided are methods of purifying and propagating packaged rAAV in embryonated avian eggs or in avian embryonic fibroblasts.

Abstract: Disclosed herein are monoclonal antibodies targeting specific tau epitopes, particularly, phosphorylated tau epitopes. Also disclosed are methods of detecting tau protein in a subject, comprising performing an assay using the antibodies or antigen binding fragments thereof on the subject or on a biological sample obtained from the subject. Assay kits containing the disclosed antibodies are also provided. Further, methods of treating or preventing a tauopathy in a subject by administering to the subject tau antibodies or antigen-binding fragments thereof are provided.

Abstract: Disclosed herein are materials and methods for the treatment of stress-related disorders and cancer. The disclosure provides an antibody, or antigen binding fragment thereof, that specifically binds to a region of corticotropin-releasing hormone (CRH). The disclosure also provides methods of treating a disorder associated with HPA axis activation, such as a stress-related disorder or cancer, comprising administering to a subject in need thereof an antibody or antigen binding fragment thereof described herein in an amount effective to treat the disorder.

Abstract: Disclosed herein are monoclonal antibodies targeting specific tau epitopes, particularly, microtubule binding domain region 2 or region 4. Also disclosed herein are antibodies or antigen binding fragments thereof that specifically recognize a tau epitope consisting of the amino acid sequence of SEQ ID NO: 9 or 11. Also disclosed herein are methods of detecting tau protein in a subject, comprising performing an assay using the antibodies or antigen binding fragments thereof on the subject or on a biological sample obtained from the subject. Assay kits containing the disclosed antibodies are also provided. Further, methods of treating or preventing a tauopathy in a subject by administering to the subject tau antibodies or antigen-binding fragments thereof are provided.

Abstract: Disclosed herein are monoclonal antibodies targeting specific tau epitopes, particularly, phosphorylated tau epitopes. Also disclosed are methods of detecting tau protein in a subject, comprising performing an assay using the antibodies or antigen binding fragments thereof on the subject or on a biological sample obtained from the subject. Assay kits containing the disclosed antibodies are also provided. Further, methods of treating or preventing a tauopathy in a subject by administering to the subject tau antibodies or antigen-binding fragments thereof are provided.

Abstract: The invention provides constructs that feature a nucleic acid molecule encoding an amino terminal region of a BRI polypeptide. A construct of the invention can further include a multiple cloning site joined to the 3? end of the BRI nucleic acid molecule or a nucleic acid molecule encoding a heterologous polypeptide operably linked to the BRI nucleic acid molecule. The invention further provides methods of directing a heterologous polypeptide through the secretory pathway in a cell. Such methods utilize a construct of the invention that additionally contains a promoter that directs expression of the BRI and heterologous nucleic acid molecules. The construct is introduced into a cell and, following expression, the fusion protein is directed through the secretory pathway of the cell. In addition, a construct of the invention can be introduced into an animal to make the animal transgenic for the heterologous polypeptide.

Abstract: The invention provides a method of preventing, delaying, or reversing the progression of Alzheimer's disease by administering an A?42 lowering agent to a mammal under conditions in which levels of A?42 are selectively reduced, levels of A?38 are increased, and levels of A?40 are unchanged. The invention provides methods and materials for developing and identifying A?42 lowering agents. In addition, the invention provides methods for identifying agents that increase the risk of developing, or hasten progression of, Alzheimer's disease. The invention also provides compositions of A?42 lowering agents and antioxidants, A?42 lowering agents and non-selective secretase inhibitors, as well as A?42 lowering agents and acetylcholinesterase inhibitors.

Abstract: The invention provides constructs that feature a nucleic acid molecule encoding an amino terminal region of a BRI polypeptide. A construct of the invention can further include a multiple cloning site joined to the 3′ end of the BRI nucleic acid molecule or a nucleic acid molecule encoding a heterologous polypeptide operably linked to the BRI nucleic acid molecule. The invention further provides methods of directing a heterologous polypeptide through the secretory pathway in a cell. Such methods utilize a construct of the invention that additionally contains a promoter that directs expression of the BRI and heterologous nucleic acid molecules. The construct is introduced into a cell and, following expression, the fusion protein is directed through the secretory pathway of the cell. In addition, a construct of the invention can be introduced into an animal to make the animal transgenic for the heterologous polypeptide.

Abstract: The invention provides a method of preventing, delaying, or reversing the progression of Alzheimer's disease by administering an A&bgr;42 lowering agent to a mammal under conditions in which levels of A&bgr;42 are selectively reduced, levels of A&bgr;38 are increased, and levels of A&bgr;40 are unchanged. The invention provides methods and materials for developing and identifying A&bgr;42 lowering agents. In addition, the invention provides methods for identifying agents that increase the risk of developing, or hasten progression of, Alzheimer's disease. The invention also provides compositions of A&bgr;42 lowering agents and antioxidants, A&bgr;42 lowering agents and non-selective secretase inhibitors, as well as A&bgr;42 lowering agents and acetylcholinesterase inhibitors.