Sembragiline: A Novel, Selective Monoamine Oxidase Type B Inhibitor for the Treatment of Alzheimer's Disease.

Monoamine oxidase B (MAO-B) has been implicated in the pathogenesis of Alzheimer's disease (AD) and other neurodegenerative disorders. Increased MAO-B expression in astroglia has been observed adjacent to amyloid plaques in AD patient brains. This phenomenon is hypothesized to lead to increased production of hydrogen peroxide and reactive oxygen species (ROS), thereby contributing to AD pathology.

Up-regulation of the isoenzymes MAO-A and MAO-B in the human basal ganglia and pons in Huntington's disease revealed by quantitative enzyme radioautography.

Huntington's disease (HD) is a rare genetic disease associated with the degeneration of GABAergic striatal projection neurons in the basal ganglia leading to movement disorders with behavioral symptoms for which there is presently no therapy. Abnormally high levels of monoamine oxidase (MAO) activity, which are potentially linked to cytotoxic free radical formation, are known to occur during aging and in neurodegenerative disorders (MAO-B is markedly increased in plaque-associated astrocytes in Alzheimer's disease). We therefore measured, with anatomical resolution, MAO-A and -B activities in 5 cases of HD (severity grades 1-3) and age-matched controls by quantitative enzyme radioautography using radiolabeled enzyme inhibitors (3)H-Ro 41-1049 and (3)H-lazabemide, respectively, as high-affinity ligands in vitro.