Progress in study on the final executor of necroptosis MLKL and its inhibitors

Area of Science:

• Molecular Biology
• Cell Biology
• Biochemistry

Background:

• Necroptosis is a regulated form of cell death.
• It involves the receptor-interacting protein kinase (RIPK) 1/RIPK3/mixed lineage kinase domain-like protein (MLKL) signaling pathway.
• MLKL acts as the final effector in necroptosis.

Purpose of the Study:

• To elucidate the multifaceted roles of MLKL in various cell death pathways.
• To explore MLKL's involvement in disease pathogenesis.
• To identify MLKL as a potential therapeutic target.

Main Methods:

• Analysis of the RIPK1/RIPK3/MLKL signaling cascade.
• Investigation of MLKL's role in membrane pore formation.
• Review of MLKL's association with NETosis, pyroptosis, and autophagy.

Main Results:

• Activated MLKL forms pores in the cell membrane, leading to cell death.
• MLKL is implicated in multiple cell death processes beyond necroptosis.
• MLKL is linked to the pathology of cardiovascular diseases, neurodegenerative diseases, and cancer.

Conclusions:

• MLKL is a crucial mediator of necroptosis and other cell death modalities.
• Understanding MLKL's functions is key to developing treatments for diseases associated with aberrant cell death.
• MLKL represents a promising therapeutic target for a range of pathologies.