User:Loganne Wertz/Sandbox1

Caspase-6 is an endopeptidase[1] involved in apoptosis. In terms of its catalytic function, it is a part of the cysteine-aspartate family [2]. Before Caspase-6 becomes functional and active, the enzyme exists as a , also known as a zymogen [3]. In solution, two zymogens are associated together, forming a homodimer. Zymogen activation, the process by which Caspase-6 becomes active, is largely conserved across the caspase family, however, Caspase-6 is unique in that it becomes active through self-cleavage rather than cleavage by a separate enzyme. Each zymogen of the unprocessed enzyme contains a consisting of two helices and subunit consisting of three helices, a , as well as an intersubunit linker. The helices surround a beta sheet core. In order to become active, the intersubunit linker is bound to the active site of Caspase-6, where it is then cleaved. After cleavage, the four processed subunits, two originating from each zymogen, remain closely associated together through intermolecular forces, forming a dimer of dimers.

Caspase-6 Protein

Medical Relevance

Caspase-6 involvement in Alzheimer's Disease

Found at high concentrations in the brain and bordering tissues, Caspase-6 has been implicated in several neurological diseases including Alzheimer's and dementia[4]^[1]. Caspase-6 activity is associated with the formation of lesions within the Alzheimer's Disease (AD)[5].Lesions can be found in early stages of AD^[1]. A proapoptotic protein, p53, is present at increased levels within AD brains, which seems to directly increase the transcription of Caspase-6, which indirectly influences apoptosis of neurons. Future treatments of AD include selective inhibition of active Caspase-6 proteins; staining has found active Caspase-6 within the hippocampus and cortex of the brain within a varying severity of AD cases. This suggests that Caspase-6 plays a predominate role in the pathophysiology of AD. There has been research conducted that shows activation of Caspase-6 in AD could cause disruption of the cytoskeleton network of neurons and lead to neuronal apoptosis^[1].