|Amyloid aggregation in programmed necrosis or necroptosis
Our lab was one of the first describing necrotic cell death as a programmed form of cell death implicated in many inflammatory and degenerative pathologies (Vandenabeele et al., 2010). Until recently, the prototype cell death mechanism has been thought to be apoptosis, which involves activation of a cascade of caspases and the consecutive cleavage of proteins. Nowadays, regulated or programmed necrosis, also called necroptosis, is viewed as another major type of cell death. Necroptosis is mainly driven by the combined action of receptor interacting protein kinase 1 (RIPK1) and RIPK3 kinases (Declercq et al., 2009). Targeting these RIP kinases by small-molecule inhibitors (necrostatins) (Degterev et al., 2008) has been proven as a powerful tool to block necrotic cell death both in vitro and in vivo.
Many stimuli can elicit necrotic cell death including pathogens, TNF family members, pathogen associated molecular patterns (PAMPs), damage associated molecular patterns (DAMPs), and also some chemotherapeutics...