Protein homeostasis (Proteostasis) (Proteostasis)

Protein homeostasis, or proteostasis, is the essential biological process that maintains the health and functionality of the cellular proteome through a balanced network of synthesis, folding, trafficking, and degradation [PubMed: 21253518]. The proteostasis network (PN) relies on molecular chaperones to assist in protein folding and specialized systems like the ubiquitin-proteasome system (UPS) and the lysosome-autophagy pathway to eliminate damaged or misfolded proteins [PubMed: 25772312]. When proteostasis is compromised—often due to aging or genetic mutations—the resulting accumulation of toxic protein aggregates leads to various pathologies, most notably neurodegenerative diseases like Alzheimer's and Parkinson's [PubMed: 29074401]. In contrast, malignant cells frequently over-rely on proteostatic pathways to survive high levels of proteotoxic stress, making specific components of this network, such as the 26S proteasome or Hsp90, effective targets for chemotherapy [PubMed: 30043516]. While 'cellular proteostasis' describes a broad physiological state rather than a single molecular target, it serves as a critical framework for developing therapies that either restore protein balance (e.g., pharmacological chaperones for cystic fibrosis) or selectively disrupt it (e.g., proteasome inhibitors for multiple myeloma) [PubChem: 387447, 53340666].

Other names

Cellular proteostasisProteostasis networkProtein quality controlProteome maintenancePN

Modulation of the proteostasis network through proteasome inhibition, chaperone induction or inhibition, autophagy stimulation, or pharmacological stabilization of misfolded proteins [PubMed: 21253518, 25772312].