A Pathogenic Mechanism Potentially Operative in Multiple Progressive Diseases and Its Therapeutic Implications

Abstract

A variety of peptide signaling moieties that we have termed intracrines can act in the interiors of their cells of synthesis or of target cells after internalization. These intracrine factors are known to be upregulated in such disorders as diabetic nephropathy, systolic heart failure, and age-related macular degeneration. Indeed, a similar set of intracrines is upregulated in each of these disorders, suggesting a commonality of mechanism. In addition, several chronic neurodegenerative disorders such as Alzheimer disease and Parkinson disease involve intercellular trafficking of intracellular disease-causing proteins. These disorders can be considered intracrine-like. Here the mechanistic and therapeutic implications of these observations, and of the relevant modes of intracrine action, are discussed, including the possibility that similar therapeutic approaches could be effective in multiple progressive disorders and the implications of these observations for intracrine pharmacology in general.