Protein Quality Control under Different Pathological Conditions

Dear Colleagues,

Maintaining proper protein homeostasis/proteostasis, i.e., the balance between protein synthesis and protein degradation, is of the utmost importance for preserving the health of our cells. There are several protein quality control (PQC) mechanisms, namely the unfolded protein response, the ubiquitin proteasome system, and the macroautophagy–lysosomal system, all of which continually assist the cells in achieving homeostasis. These pathways are evolutionarily conserved and are responsible for maintaining correct protein conformation and clearing superfluous, damaged, and/or dysregulated proteins. However, under various pathological conditions, including aging, cardiovascular and neurological disorders, and cancer, the normal functioning of these pathways decline, causing protein synthesis to exceed degradation. These failed PQC systems lead to the accumulation of damaged/misfolded proteins (also known as proteotoxicity), leading to cell and organ damage.

Notably, post-mitotic cells, including neurons and cardiomyocytes with a limited proliferative capacity, are heavily reliant on the PQC pathways and are adversely influenced by their impairment. An evolving hypothesis is that the suppression of PQC pathways is not only causal but also contributes to the acceleration of disease processes. Thus, a better understanding of the molecular mechanisms involved in these PQC pathways during the onset and throughout the pathological episode is needed. Targeting PQC systems might prove to be a feasible therapeutic strategy to delay the onset of disease, reduce the severity, or even prevent the development of various pathological conditions. We welcome papers on topics that include, but are not limited to, the following:

• Current advances in the field of protein quality control systems in various cells and tissues under different pathophysiological conditions;
• Novel methods available for monitoring PQC mechanisms;
• Targeting the PQC pathways to ameliorate different pathologies;
• PQC mechanisms during aging.

Dr. Rajeshwary Ghosh
Guest Editor

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• proteasome
• autophagy
• disease