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Nat. Rev. Neurol. doi:10.1038/nrneurol.2017.99 Figure 1 Protein aggregates in tissue from patients with neurodegenerative disease Figure 1 | Protein aggregates in tissue from patients with neurodegenerative disease. Most neurodegenerative diseases have distinct clinical manifestations, but they share accumulation of protein aggregates and inclusions that contain specific proteins in distinct brain regions; these aggregates are associated with an endoplasmic reticulum stress reaction. PDI, protein disulfide isomerase; p, phosphorylated; PERK, protein kinase RNA-like ER kinase; IRE1, inositol-requiring protein 1. Part a reproduced with permission from John Wiley and Sons © Nijholt, D. A. et al. J. Pathol. 226, 693–702 (2012). Part b reproduced with permission from Elsevier © Jeroen, J. M. et al. Am. J. Pathol. 174, 1241–1251 (2009). Part c reproduced with permission from BioMed Central © Stutzbach, L. D. et al. Acta Neuropathol. Commun. 1, 31 (2013). Part d reproduced with permission from Elsevier © Hoozemans, J. J. et al. Biochem. Biophys. Res. Commun. 354, 707–711 (2007) (left and middle panels) and © Conn, K. J. et al. Brain Res. 1022, 164–172 (2004) (right panel). Part e reproduced with permission from Elsevier © Atkin, J. D. et al. Neurobiol. Dis. 30, 400–407 (2008) (left panel) and © Ito, Y. et al. Neurobiol. Dis. 36, 470–476 (2009) (right panel). Part a reproduced with permission from John Wiley and Sons © Nijholt, D. A. et al. J. Pathol. 226, 693–702 (2012). Part b reproduced with permission from Elsevier © Jeroen, J. M. et al. Am. J. Pathol. 174, 1241–1251 (2009). Part c reproduced with permission from BioMed Central © Stutzbach, L. D. et al. Acta Neuropathol. Commun. 1, 31 (2013). Part d reproduced with permission from Elsevier © Hoozemans, J. J. et al. Biochem. Biophys. Res. Commun. 354, 707–711 (2007) (left and middle panels) and © Conn, K. J. et al. Brain Res. 1022, 164–172 (2004) (right panel). Part e reproduced with permission from Elsevier © Atkin, J. D. et al. Neurobiol. Dis. 30, 400–407 (2008) (left panel) and © Ito, Y. et al. Neurobiol. Dis. 36, 470–476 (2009) (right panel). Hetz, C. & Saxena, S. (2017) ER stress and the unfolded protein response in neurodegeneration Nat. Rev. Neurol. doi:10.1038/nrneurol.2017.99