Abstract: As disclosed herein, ?-arrestin1 and ?-arrestin2 levels are highly elevated in brains of FTLD-tau patients suggesting that both ?-arrestin1 and ?-arrestin2 are elevated in the brains of patients with AD and FLTD. The current work also shows that when ?-arrestin2 is overexpressed, tau levels become elevated. The data indicate that ?-arrestin2 reduces tau clearance by impairing p62-mediated autophagy, a role carried out by the oligomerized form of ?-arrestin2. Therefore, disclosed herein are ?-arrestin oligomerization inhibitors that can be used to prevent ?-arrestin oligomerization and therefore the accumulation of tau in cells, i.e. tauopathy. Also disclosed are methods of treating a tauopathy in a subject that involve administering to the subject a therapeutically effective amount of a ?-arrestin oligomerization inhibitor disclosed herein.

Abstract: As disclosed herein, ?-arrestin1 and ?-arrestin2 levels are highly elevated in brains of FTLD-tau patients suggesting that both ?-arrestin1 and ?-arrestin2 are elevated in the brains of patients with AD and FLTD. The current work also shows that when ?-arrestin2 is overexpressed, tau levels become elevated. The data indicate that ?-arrestin2 reduces tau clearance by impairing p62-mediated autophagy, a role carried out by the oligomerized form of ?-arrestin2. Therefore, disclosed herein are ?-arrestin oligomerization inhibitors that can be used to prevent ?-arrestin oligomerization and therefore the accumulation of tau in cells, i.e. tauopathy. Also disclosed are methods of treating a tauopathy in a subject that involve administering to the subject a therapeutically effective amount of a ?-arrestin oligomerization inhibitor disclosed herein.

Abstract: Disclosed herein are compounds, compositions, and methods for selecting targeting ?2AR receptors. The compounds, compositions, and methods may be used in the treatment of obstructive lung diseases.

Abstract: Methods and compositions for diagnosing and treating diseases are provided. The methods involve the discovery of a correlation between an ?2C-adrenergic receptor gene polymorphism, a combination of polymorphisms or a haplotype and the occurrence of diseases such as heart failure, cardiac arrhythmias, hypertension, behavioral and learning disorders, psychiatric diseases such as depression, obesity, and diabetes mellitus. The invention further pertains to the use of such molecules and methods in the diagnosis, prognosis, and treatment selection for diseases such as heart failure, cardiac arrhythmias, hypertension, behavioral and learning disorders, psychiatric diseases such as depression, obesity, and diabetes mellitus. The invention also pertains to a composition of matter comprising polymorphisms and haplotypes of the ?2C-adrenergic receptor.

Abstract: Methods and compositions for the detection, diagnosis, and prevention of cardiac conditions are provided. Polymorphisms of ?1-adrenergic receptor are provided. The Gly389 ?1-adrenergic receptor variants are not as responsive to treatment ? blockers such as carvedilol, metoprolol or bisoprol. Thus, genotyping ?1-adrenergic receptor polymorphisms is useful for predicting relative responsiveness to treatment with beta blockers. The Gly389 polymorphism also may be used, alone or in conjunction with other adrenergic receptor polymorphisms, to predict relative risk of developing cardiovascular diseases such as heart failure or to predict relative survival rate in patients with heart failure or other cardiovascular diseases. Also provided are transgenic mice and transgenic cells expressing the ?1-adrenergic receptor polymorphisms, and their use in identifying therapeutic agents.

Abstract: The present invention provides methods to protect a subject from a respiratory disorder involving an airway obstructive disease such as asthma or chronic obstructive pulmonary disease. Provided are methods to protect a subject from an airway obstructive disease using gene therapy. &bgr;2-adrenergic receptors (&bgr;2AR) act to relax airway smooth muscle and can serve to counteract hyperresponsiveness. Methods are provided for supplying &bgr;2AR function to cells of the lung and airway, such as smooth muscle and epithelial cells, by &bgr;2AR gene therapy. The &bgr;2AR gene, a modified &bgr;2AR gene, or a part of the gene may be introduced into the cell in a vector such that the gene remains extrachromosomal or may be integrated into the subjects chromosomal DNA for expression. These methods provide for administering to a subject in need of such treatment a therapeutically effective amount of a &bgr;2AR gene, or pharmaceutically acceptable composition thereof, for overexpressing the &bgr;2AR gene.

Abstract: The invention concerns polymorphisms in the &bgr;1- and the &bgr;2-adrenergic receptors. The invention also pertains to methods and molecules for detecting such polymorphisms. The invention further pertains to the use of such molecules and methods in the diagnosis, prognosis, and treatment selection for cardiovascular diseases, obesity, and diabetes.