PADmediated

PADmediated refers to cellular or molecular processes governed by the family of enzymes known as peptidylarginine deiminases (PADs). These enzymes catalyze citrullination, a post-translational modification that converts arginine residues in target proteins into citrulline, altering charge, structure, and function.

PAD activity is calcium-dependent and increases under conditions that elevate intracellular calcium. PAD4 is primarily nuclear, whereas other PAD isoforms are located in the cytosol or cytoskeleton. Citrullination can affect histones, cytoskeletal proteins, enzymes, and extracellular matrix components, influencing chromatin structure, protein interactions, and cytoskeletal dynamics. In some immune cells, PAD-mediated citrullination contributes to the formation of neutrophil extracellular traps (NETs).

In human disease, PAD-mediated citrullination is best studied in autoimmune conditions, particularly rheumatoid arthritis, in which citrullinated proteins become targets of autoantibodies. Aberrant PAD activity has also been linked to inflammatory and neurodegenerative disorders in various studies, though causal relationships are not yet established. The term PADmediated is used to describe mechanisms that depend on PAD-catalyzed citrullination.

Detection and study of PADmediated processes use biochemical assays of PAD activity, mass spectrometry to identify citrullinated sites, and serologic tests for anti-citrullinated protein antibodies. Pharmacologic inhibitors of PADs, such as Cl-amidine and selective PAD4 inhibitors, are used in preclinical work to assess therapeutic potential, with ongoing research into safety and efficacy.

Overall, PADmediated processes refer to a class of post-translational modifications with relevance to development, immunity, and disease, and remain an active area of biomedical research.