Proteostatisen

Proteostasis refers to the intricate biological process of maintaining the stability and functional integrity of the proteome, the entire set of proteins expressed by an organism or cell. This involves a delicate balance between the synthesis, folding, trafficking, and degradation of proteins. Proteostasis is crucial for cellular health and function, as misfolded or aggregated proteins can lead to a variety of diseases, including neurodegenerative disorders like Alzheimer's and Parkinson's, as well as cancer and metabolic diseases.

Key mechanisms contributing to proteostasis include the endoplasmic reticulum (ER) unfolded protein response (UPR), molecular chaperones that assist in proper protein folding, and cellular machinery responsible for protein degradation, such as the ubiquitin-proteasome system (UPS) and autophagy. The UPR is activated when the ER senses an accumulation of unfolded or misfolded proteins, initiating a cascade of events to restore homeostasis by increasing chaperone production or triggering cell death if the stress is too severe. Chaperones bind to nascent or stressed proteins, preventing aggregation and promoting correct folding pathways.

When proteins become terminally damaged or misfolded, they are targeted for degradation. The UPS marks proteins with ubiquitin tags, directing them to the proteasome for breakdown into smaller peptides. Autophagy is a more general cellular recycling process that engulfs larger protein aggregates or damaged organelles for lysosomal degradation. Dysregulation of any of these pathways can lead to proteostasis collapse, contributing to cellular dysfunction and disease. Research into proteostasis aims to understand these complex networks and develop therapeutic strategies to correct proteostatic imbalances.