Proteostasis

Proteostasis is the dynamic regulation of a balanced, functional proteome. The proteostasis network includes competing and integrated biological pathways within cells that control the biogenesis, folding, trafficking, and degradation of proteins present within and outside the cell.[1][2] Loss of proteostasis is central to understanding the cause of diseases associated with excessive protein misfolding and degradation leading to loss-of-function phenotypes,[3] as well as aggregation-associated degenerative disorders.[4] Therapeutic restoration of proteostasis may treat or resolve these pathologies.[5]

Cellular proteostasis is key to ensuring successful development, healthy aging, resistance to environmental stresses, and to minimize homeostatic perturbations from pathogens such as viruses.[2] Cellular mechanisms for maintaining proteostasis include regulated protein translation, chaperone assisted protein folding, and protein degradation pathways. Adjusting each of these mechanisms based on the need for specific proteins is essential to maintain all cellular functions relying on a correctly folded proteome.

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  2. ^ a b Balch WE, Morimoto RI, Dillin A, Kelly JW (February 2008). "Adapting proteostasis for disease intervention". Science. 319 (5865): 916–9. Bibcode:2008Sci...319..916B. doi:10.1126/science.1141448. PMID 18276881. S2CID 20952037.
  3. ^ Mu TW, Ong DS, Wang YJ, Balch WE, Yates JR, Segatori L, Kelly JW (September 2008). "Chemical and biological approaches synergize to ameliorate protein-folding diseases". Cell. 134 (5): 769–81. doi:10.1016/j.cell.2008.06.037. PMC 2650088. PMID 18775310.
  4. ^ Cohen E, Paulsson JF, Blinder P, Burstyn-Cohen T, Du D, Estepa G, et al. (December 2009). "Reduced IGF-1 signaling delays age-associated proteotoxicity in mice". Cell. 139 (6): 1157–69. doi:10.1016/j.cell.2009.11.014. PMC 3017511. PMID 20005808.
  5. ^ Djajadikerta A, Keshri S, Pavel M, Prestil R, Ryan L, Rubinsztein DC (April 2020). "Autophagy Induction as a Therapeutic Strategy for Neurodegenerative Diseases". Journal of Molecular Biology. Autophagy in Neurodegenerative Diseases. 432 (8): 2799–2821. doi:10.1016/j.jmb.2019.12.035. PMID 31887286. S2CID 209518157.