Extracellular protein homeostasis: The dawning of a new age for human disease therapies?

Abstract

In all these situations, misfolded proteins (or resulting PGPFs) are taken up by cells via receptor-mediated endocytosis and directed to lysosomes for degradation. gl Extracellular chaperones (ECs) are central components of the extracellular protein homeostasis system (Figure 1). The translation of our growing understanding of extracellular protein homeostasis into effective new treatments for diseases associated with protein misfolding and aggregation, many of which are still intractable, is a goal with potentially huge future benefits for global health. The protein homeostasis (proteostasis) system consists in a network of processes that governs the synthesis, folding, concentration, trafficking and degradation of proteins.[1] The maintenance of protein homeostasis is especially important in extracellular spaces, where protein molecules are constantly exposed to oxidizing agents, large variations in pH and ionic strength, and mechanical and thermal stresses associated with fluid circulation (Figure 1). [Extracted from the article]