Molecular Perspective on Proteases: Regulation of Programmed Cell Death Signaling, Inflammation and Pathological Outcomes

Proteases are essential enzymes that regulate numerous physiological processes and cellular signaling networks to maintain homeostasis and cellular fate. This regulation is mediated by a group of proteases with the primary function of cleaving peptide bonds, thereby modulating the activity of proteins for vital functions and influencing various cellular and physiological functions including digestion, absorption, cellular signaling, apoptosis, inflammation, immune response, cell growth, differentiation, cell death, and reproduction. Proteases define the fate of cells by modulating the downstream signal transduction pathways for modalities of cell death known as apoptosis, necroptosis, pyroptosis, and autophagy. Similarly, during inflammatory stimulation, proteases orchestrate a cascade of pathways that optimize the immune response to pathogens. Proteases play a crucial role in the pathogenesis of various human diseases, including cancer, metabolic, inflammatory, and neurological disorders. The activation of specific proteases determines the outcomes of different forms of cell death inflammation and imbalance may cause various pathological manifestations highlighted in this review. Understanding protease-mediated signaling mechanisms is therefore vital for elucidating disease pathogenesis and identifying potential therapeutic targets.