Nekroptoosi

Nekroptoosi, also known as programmed necrosis, is a regulated form of cell death. Unlike apoptosis, which is an active and often programmed process of cell self-destruction, nekroptoosi is characterized by cell swelling and membrane rupture. It is triggered by specific signaling pathways and involves the activation of a complex of proteins known as the RIPK1-RIPK3-MLKL necrosome.

The molecular machinery of nekroptoosi is initiated when certain death receptors or pattern recognition receptors are activated. This leads to the recruitment of receptor-interacting protein kinase 1 (RIPK1) and receptor-interacting protein kinase 3 (RIPK3) to form a necrosome. Subsequently, mixed lineage kinase domain-like protein (MLKL) is phosphorylated by RIPK3, leading to its oligomerization and translocation to the plasma membrane. Once at the membrane, MLKL forms pores that disrupt its integrity, causing the cell to swell and ultimately lyse.

Nekroptoosi plays a crucial role in immunity, particularly in eliminating infected cells and in the inflammatory response. It can also be involved in various pathological conditions, including inflammatory diseases, ischemia-reperfusion injury, and neurodegeneration. While often considered a pro-inflammatory form of cell death due to the release of cellular contents, research is ongoing to fully elucidate its diverse functions and therapeutic implications. The distinct morphological and molecular features differentiate it from other forms of programmed cell death.