Proteostasis pathway (PN) (PN)

The proteostasis pathway, or proteostasis network (PN), is an integrated system of biological pathways that control the biogenesis, folding, trafficking, and degradation of proteins within and outside the cell (Balch et al., Science, 2008). This network ensures that the proteome is correctly folded and functional, preventing the accumulation of misfolded or aggregated proteins which are toxic to cells (Labbadia & Morimoto, Nature Reviews Molecular Cell Biology, 2015). Key components of the PN include molecular chaperones, the ubiquitin-proteasome system (UPS), and the autophagy-lysosome pathway (Hipp et al., Nature, 2019). Dysregulation of proteostasis is a hallmark of numerous diseases, particularly neurodegenerative conditions like Alzheimer's and Parkinson's, where protein aggregation occurs, and cancer, where cells often hijack proteostasis to survive proteotoxic stress (Hipp et al., Nature Reviews Molecular Cell Biology, 2014). Therapeutic strategies targeting this pathway involve either enhancing the capacity of the network through chaperone inducers or kinetic stabilizers, or inhibiting specific nodes like the proteasome to induce apoptosis in malignant cells (Powers et al., Annual Review of Biochemistry, 2009). By modulating these processes, researchers aim to restore cellular health in protein-misfolding diseases or selectively eliminate diseased cells (Klaips et al., Journal of Biological Chemistry, 2018).

Other names

Protein homeostasis networkProteostasis networkPN

Modulation of protein folding, degradation, and trafficking through various nodes including the ubiquitin-proteasome system, autophagy-lysosome pathway, and molecular chaperones (Powers et al., Annual Review of Biochemistry, 2009).