Methods for treating, preventing and reducing the progression of neurodegenerative and neurological diseases, including, without limitation Alzheimer's disease, are provided. The methods of the invention inhibit one or both of TIM-1 and P-selectin function and reduce leukocyte and platelet cell adhesion, activation and interaction with the vascular endothelium and infiltration of leukocytes into the brain.

The present disclosure describes peptide inhibitors of Rho-associtated-kinase (ROCK) and their use in treating disorders including heart failure, the leading cause of combined morbidity and mortality in the United States. An inhibitory polypeptide blocks ROCK1 activity in the presence of 1 mM ATP. The binding epitope on ROCK1 was mapped using chemical cross-linking to the Activation Loop, a novel locus identifying a new class of inhibitory drugs. The peptides described will be useful against a number of important diseases such as heart disease, pulmonary hypertension, arterial hypertension, gluacoma management, insulin resistance, kidney disease, hemolytic anemia, stroke, ischemia reperfusion injury, or acute mycloid leukemia.

In various implementations, berberine metabolites, such as dihydroberberine and/or tetrahydroberberine, may be administered to manage blood glucose levels, increase ketone levels (e.g., blood concentration of ketones), and/or for therapeutic purposes in humans. The administration of a pharmaceutically effective amount of berberine metabolites, such as dihydroberberine, may reduce fasting blood glucose levels, improve glucose tolerance, and/or improve blood ketone response. In some implementations, berberine metabolites may be administered with one or more other compounds.

Provided are methods of treating a cancer characterized by the presence of a mutant allele of IDH1/2 comprising administering to a subject in need thereof a compound described here.

The present invention is based, in part, on the discovery of peptide tags that increase the half-life and/or mean residence time of proteins or nucleic acids in the eye. In certain aspects the invention peptide tags increase the half-life and/or mean residence time of antibodies and antigen binding fragments, therapeutic proteins, protein receptors, DARPins and/or aptamers in the eye.

This invention relates to the use of an agent capable of inhibiting IL-36 proteolytic processing for the treatment and/or reduction of inflammation in a subject. Advantageously, the agent prevents the production of a biologically active IL-36 to prevent and/or reduce the pro-inflammatory effects of IL-36. The invention also relates to a method for treatment and/or reduction of inflammation and compositions for treating and/or reducing inflammation.

This invention is related to the field of PCSK9 biology and the composition and methods of use of small molecule ligands for modulation of PCSK9 biological activity. In particular, the invention provides compositions of small molecule compounds that modulate circulating levels of low density lipoproteins by altering the conformation of the protein PCSK9. Binding these small molecule ligands to PCSK9 alters the conformation of the protein, modifying the interaction between PCSK9 and an endogenous low density lipoprotein receptor, and can lead to reduced or increased levels of circulating LDL-cholesterol. High LDL-cholesterol levels are associated with increased risk for heart disease. Low LDL-cholesterol levels may be problematic in other conditions, such as liver dysfunction; thus, there is also utility for small molecule ligands that can raise LDL levels.

The present invention provides compounds, compositions thereof, and methods of using the same.

The present invention relates to a method for treating degenerative neurological disorders in a subject in need thereof, comprising administering to a subject in need thereof a therapeutically effective amount of a composition comprising an acid sphingomyelinase (ASM) activity inhibitor or expression inhibitor as an active ingredient.

Methods and compositions are provided for treating or preventing a neurological disease or disorder using an inhibitor of Glyoxalase 1 (GLO1). In some embodiments, the inhibitor is a small molecule. In certain embodiments, the disease or disorder is a sleep disorder, a mood disorder such as depression, epilepsy, an anxiety disorder, substance abuse, substance dependence or substance such as an alcohol withdrawal syndrome.