Caspase-6 is classified as an endopeptidase[1] involved in apoptosis. In terms of its catalytic function, it is a part of the cysteine-aspartate family [2]. It's primarily involved in apoptosis through a largely ambiguous mechanism. Before Caspase-6 is a functional and active dimer, the enzyme exists as a , also known as zymogen [3]. Zymogen activation 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. The unprocessed enzyme exists as a dimer and contains a and subunit, a , as well as an intersubunit linker. To become active, the intersubunit linker binds to the active site, where it is then cleaved.
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].
