BACKGROUND OF THE INVENTION

Caspases comprise a family of cysteine protease enzymes with a well-known role as key mediators in apoptosis signaling pathways and cell disassembly. Interleukin converting enzyme (ICE), also known as Caspase-1, was the first identified caspase. In humans, 11 other known caspases have been further identified. Caspases have been classified in two general groups according to their effects: proapoptotic (caspase-2, 3, 6, 7, 8, 9, 10) and proinflammatory (caspase-1, 4, 5, 11, 12) caspases. The proapoptotic caspases have been divided in initiators (caspase-2, 8, 9, 10) also known as group II, and executioners (caspase-3, 6, 7) of the apoptotic process or group III. The Interleukin converting enzyme (ICE), also known as Caspase-1, appears to have a proinflammatory role only.

There is growing evidence demonstrating the role of caspases in very diverse pathologies. For instance, increased levels of apoptosis and caspase activity are reported to be frequently observed at sites of cellular damage in both acute (e.g., Sepsis, myocardial infarction (MI), Ischemic Stroke, Spinal cord injury (SCI), traumatic Brain Injury (TBI)) and neurodegenerative disease (e.g. Alzheimer's, Parkinson's and Huntington's diseases, and multiple sclerosis (MS)). And because of the significant impact of such diverse pathologies on the world's population, and the apparent paucity of therapeutic agents that treat those pathologies by targeting (e.g., inhibiting) caspases (e.g., caspase-6), there is a need for compounds designed for inhibiting caspases. Capsase-6 plays a central role in the development and pathology of several neurodegenerative diseases including Alzheimer's and Huntington's diseases, due to cleavage of microtubule associated protein Tau and polygluatimine expanded huntingtin protein.

