Extracellular and Organismal Proteostasis

Dear Colleagues,

Our current understanding of the mechanisms that operate to maintain protein homeostasis (proteostasis) in spaces outside cells in the body is surprisingly limited. A failure or dysfunction in these processes leads to physiologically dangerous levels of misfolded, aggregated and potentially cytotoxic extracellular proteins, resulting in the development of a variety of serious human diseases and which may contribute directly to the ageing process. The identification of a small but growing family of constitutively secreted extracellular chaperones (ECs) is one important step towards a better understanding of extracellular proteostasis. These secreted ECs are found in body fluids at concentrations in the μg/mL to mg/mL range, and are thought to recognise and specifically bind to extracellular misfolded proteins to maintain their solubility, neutralise their toxicity, and mediate their safe disposal. However, it is almost certain that other yet to be discovered processes play important roles in maintaining proteostasis in body fluids and the organism as a whole. Advances that increase our understanding in these areas are essential for the future development of strategies to treat currently incurable diseases.

The goal of this Special Issue is to present current knowledge of the mechanisms operating in extracellular and organismal proteostasis and to identify important knowledge gaps in the field.

Prof. Mark R. Wilson
Guest Editor

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