Apoptosis is the programmed cell death, triggered by a family of cysteine proteases called caspases (Behl, 2000). Caspases can inactivate vital cellular proteins that protect living cell from apoptosis (e.g. inhibitor of caspase-activated deoxyribonuclease, Bcl-2 family etc..) (Adams & Cory, 1998; Enari et al., 1998). Caspases can also cleave the proteins that regulate cytoskeleton, therefore alter the structure of the cell (Yin & Stull, 1999).
|Involvement in Alzheimer's disease|
Caspase-3 has been shown to directly cleave APP (Gervais et al., 1999). Caspase-3 mediated APP cleavage also stabilises the Beta-secretase, BACE, which facilitates the production of Abeta (Tesco et al., 2007).
Caspase not only contributes to the generation of Abeta, it also mediates the toxicity of Abeta, as research show that Abeta exposure induces activation of caspase-3 and apoptosis in cultured cortical neurons (Marín et al., 2000; Nishimura et al., 2002).
Finally, caspases provide a link between Abeta and tauopathy, as the activations of caspases result in tau cleavage (Cotman, Poon, Rissman, & Blurton-Jones, 2005), which leads to tau pathological filaments (Cho & Johnson, 2004; Gamblin et al., 2003). However, despite the growing number of evidence showing that apoptosis contributes to AD onset and progress in in vitro and transgenic animal model, its direct role in human post-mortem AD brain is still under debate.