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Annual Review of Biochemistry

Volume 86, 2017

Protein Misfolding Diseases

Abstract

The majority of protein molecules must fold into defined three-dimensional structures to acquire functional activity. However, protein chains can adopt a multitude of conformational states, and their biologically active conformation is often only marginally stable. Metastable proteins tend to populate misfolded species that are prone to forming toxic aggregates, including soluble oligomers and fibrillar amyloid deposits, which are linked with neurodegeneration in Alzheimer and Parkinson disease, and many other pathologies. To prevent or regulate protein aggregation, all cells contain an extensive protein homeostasis (or proteostasis) network comprising molecular chaperones and other factors. These defense systems tend to decline during aging, facilitating the manifestation of aggregate deposition diseases. This volume of the contains a set of three articles addressing our current understanding of the structures of pathological protein aggregates and their associated disease mechanisms. These articles also discuss recent insights into the strategies cells have evolved to neutralize toxic aggregates by sequestering them in specific cellular locations.

Keyword(s): amyloid, molecular chaperone, neurodegenerative disease, protein aggregation, protein folding, protein homeostasis, protein misfolding, proteostasis
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/content/journals/10.1146/annurev-biochem-061516-044518
2017-06-20
2025-04-20
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Literature Cited

  1. Anfinsen CB. 1.  1973. Principles that govern the folding of protein chains. Science 181:223–30 [Google Scholar]
  2. Dobson CM, Šali A, Karplus M. 2.  1998. Protein folding: a perspective from theory and experiment. Angew. Chem. Int. Ed. Engl. 37:868–93 [Google Scholar]
  3. Balchin D, Hayer-Hartl M, Hartl FU. 3.  2016. In vivo aspects of protein folding and quality control. Science 353:aac4354 [Google Scholar]
  4. Balch WE, Morimoto RI, Dillin A, Kelly JW. 4.  2008. Adapting proteostasis for disease intervention. Science 319:916–19 [Google Scholar]
  5. Brehme M, Voisine C, Rolland T, Wachi S, Soper JH. 5.  et al. 2014. A chaperome subnetwork safeguards proteostasis in aging and neurodegenerative disease. Cell Rep 9:1135–50 [Google Scholar]
  6. Hipp MS, Park S-H, Hartl FU. 6.  2014. Proteostasis impairment in protein-misfolding and -aggregation diseases. Trends Cell Biol 24:506–14 [Google Scholar]
  7. Sahni N, Yi S, Taipale M, Fuxman Bass Juan I, Coulombe-Huntington J. 7.  et al. 2015. Widespread macromolecular interaction perturbations in human genetic disorders. Cell 161:647–60 [Google Scholar]
  8. Labbadia J, Morimoto RI. 8.  2015. The biology of proteostasis in aging and disease. Annu. Rev. Biochem. 84:435–64 [Google Scholar]
  9. Douglas PM, Dillin A. 9.  2010. Protein homeostasis and aging in neurodegeneration. J. Cell Biol. 190:719–29 [Google Scholar]
  10. Chiti F, Dobson CM. 10.  2006. Protein misfolding, functional amyloid, and human disease. Annu. Rev. Biochem. 75:333–66 [Google Scholar]
  11. Astbury WT, Dickinson S, Bailey K. 11.  1935. The X-ray interpretation of denaturation and the structure of the seed globulins. Biochem. J. 29:102351–2360.1 [Google Scholar]
  12. Chiti F, Dobson CM. 12.  2017. Protein misfolding, amyloid formation, and human disease: a summary of progress over the last decade. Annu. Rev. Biochem. 86:27–68 [Google Scholar]
  13. Fandrich M, Dobson CM. 13.  2002. The behaviour of polyamino acids reveals an inverse side chain effect in amyloid structure formation. EMBO J 21:5682–90 [Google Scholar]
  14. Eisenberg DS, Sawaya MR. 14.  2017. Structural studies of amyloid proteins at the molecular level. Annu. Rev. Biochem. 86:69–95 [Google Scholar]
  15. Nelson R, Sawaya MR, Balbirnie M, Madsen AO, Riekel C. 15.  et al. 2005. Structure of the cross-β spine of amyloid-like fibrils. Nature 435:773–78 [Google Scholar]
  16. Olzscha H, Schermann SM, Woerner AC, Pinkert S, Hecht MH. 16.  et al. 2011. Amyloid-like aggregates sequester numerous metastable proteins with essential cellular functions. Cell 144:67–78 [Google Scholar]
  17. Kim YE, Hosp F, Frottin F, Ge H, Mann M. 17.  et al. 2016. Soluble oligomers of polyQ-expanded Huntingtin target a multiplicity of key cellular factors. Mol. Cell 63:951–64 [Google Scholar]
  18. Freibaum BD, Lu Y, Lopez-Gonzalez R, Kim NC, Almeida S. 18.  et al. 2015. GGGGCC repeat expansion in C9orf72 compromises nucleocytoplasmic transport. Nature 525:129–33 [Google Scholar]
  19. Woerner AC, Frottin F, Hornburg D, Feng LR, Meissner F. 19.  et al. 2016. Cytoplasmic protein aggregates interfere with nucleocytoplasmic transport of protein and RNA. Science 351:173–76 [Google Scholar]
  20. Choe YJ, Park SH, Hassemer T, Körner R, Vincenz-Donnelly L. 20.  et al. 2016. Failure of RQC machinery causes protein aggregation and proteotoxic stress. Nature 531:191–95 [Google Scholar]
  21. Park SH, Kukushkin Y, Gupta R, Chen T, Konagai A. 21.  et al. 2013. PolyQ proteins interfere with nuclear degradation of cytosolic proteins by sequestering the Sis1p chaperone. Cell 154:134–45 [Google Scholar]
  22. Yonashiro R, Tahara EB, Bengtson MH, Khokhrina M, Lorenz H. 22.  et al. 2016. The Rqc2/Tae2 subunit of the ribosome-associated quality control (RQC) complex marks ribosome-stalled nascent polypeptide chains for aggregation. eLife 5:e11794 [Google Scholar]
  23. Ciryam P, Tartaglia GG, Morimoto RI, Dobson CM, Vendruscolo M. 23.  2013. Widespread aggregation and neurodegenerative diseases are associated with supersaturated proteins. Cell Rep 5:781–90 [Google Scholar]
  24. Oromendia AB, Dodgson SE, Amon A. 24.  2012. Aneuploidy causes proteotoxic stress in yeast. Genes Dev 26:2696–708 [Google Scholar]
  25. Walther DM, Kasturi P, Zheng M, Pinkert S, Vecchi G. 25.  et al. 2015. Widespread proteome remodeling and aggregation in aging C.elegans. Cell 161:919–32 [Google Scholar]
  26. Sontag EM, Samant RS, Frydman J. 26.  2017. Mechanisms and functions of spatial protein quality control. Annu. Rev. Biochem. 86:97–122 [Google Scholar]
  27. Mogk A, Bukau B. 27.  2017. Role of sHsps in organizing cytosolic protein aggregation and disaggregation. Cell Stress Chaperones In press. doi: 10.1007/s12192-017-0762-4 [Google Scholar]
  28. Arrasate M, Mitra S, Schweitzer ES, Segal MR, Finkbeiner S. 28.  2004. Inclusion body formation reduces levels of mutant huntingtin and the risk of neuronal death. Nature 431:805–10 [Google Scholar]
  29. Kaganovich D, Kopito R, Frydman J. 29.  2008. Misfolded proteins partition between two distinct quality control compartments. Nature 454:1088–95 [Google Scholar]
  30. Johnston JA, Ward CL, Kopito RR. 30.  1998. Aggresomes: a cellular response to misfolded proteins. J. Cell Biol. 143:1883–98 [Google Scholar]
  31. Miller SB, Ho CT, Winkler J, Khokhrina M, Neuner A. 31.  et al. 2015. Compartment-specific aggregases direct distinct nuclear and cytoplasmic aggregate deposition. EMBO J 34:778–97 [Google Scholar]
/content/journals/10.1146/annurev-biochem-061516-044518
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Protein Misfolding Diseases
Annual Review of Biochemistry 86, 21 (2017); https://doi.org/10.1146/annurev-biochem-061516-044518
/content/journals/10.1146/annurev-biochem-061516-044518
/content/journals/10.1146/annurev-biochem-061516-044518
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  • Article Type: Review Article

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