Linking the Endoplasmic Reticulum to Parkinson's Disease and Alpha-Synucleinopathy

Emanuela Colla, Emanuela Colla

Abstract

Accumulation of misfolded proteins is a central paradigm in neurodegeneration. Because of the key role of the endoplasmic reticulum (ER) in regulating protein homeostasis, in the last decade multiple reports implicated this organelle in the progression of Parkinson's Disease (PD) and other neurodegenerative illnesses. In PD, dopaminergic neuron loss or more broadly neurodegeneration has been improved by overexpression of genes involved in the ER stress response. In addition, toxic alpha-synuclein (αS), the main constituent of proteinaceous aggregates found in tissue samples of PD patients, has been shown to cause ER stress by altering intracellular protein traffic, synaptic vesicles transport, and Ca2+ homeostasis. In this review, we will be summarizing evidence correlating impaired ER functionality to PD pathogenesis, focusing our attention on how toxic, aggregated αS can promote ER stress and cell death.

Keywords: ER stress; Parkinson’s disease; UPR; alpha-synuclein; alpha-synuclein aggregates; alpha-synucleinopathy; misfolded proteins.

Figures

FIGURE 1
FIGURE 1
The unfolded protein response cascade. Stressful conditions due to starvation, infections, oxidative damage, and changes in ER Ca2+ concentration can lead to accumulation of misfolded proteins in the ER. Induction of the unfolded proteins response through the activation of its three independent arms (PERK, IRE1, and ATF6) counteracts the build-up of misfolded proteins and improves the ER folding capacity.
FIGURE 2
FIGURE 2
Activation of the UPR by toxic αS. Accumulation of toxic αS in neurons directly affects cellular secretion and proteins traffic at multiple stages thanks to the ability of αS to bind synaptic vesicles and biological membranes. This traffic defect appears to be transferred progressively from the synapse to the Golgi/ER compartments, resulting in a toxic build up of misfolded proteins with concomitant activation of the UPR. Depletion of ER Ca2+ level, mediated by direct binding of αS aggregates to SERCA, an ER Ca2+ channel, or indirectly through mitochondria impairment increases cytosolic Ca2+ and exacerbates ER dysfunction.

References

    1. Acosta-Alvear D., Zhou Y., Blais A., Tsikitis M., Lents N. H., Arias C., et al. (2007). XBP1 controls diverse cell type- and condition-specific transcriptional regulatory networks. Mol. Cell 27 53–66. 10.1016/j.molcel.2007.06.011
    1. Afrazi A., Branca M. F., Sodhi C. P., Good M., Yamaguchi Y., Egan C. E., et al. (2014). Toll-like receptor 4-mediated endoplasmic reticulum stress in intestinal crypts induces necrotizing enterocolitis. J. Biol. Chem. 289 9584–9599. 10.1074/jbc.M113.526517
    1. B’chir W., Maurin A.-C., Carraro V., Averous J., Jousse C., Muranishi Y., et al. (2013). The eIF2α/ATF4 pathway is essential for stress-induced autophagy gene expression. Nucleic Acids Res. 41 7683–7699. 10.1093/nar/gkt563
    1. Belal C., Ameli N. J., El Kommos A., Bezalel S., Al’Khafaji A. M., Mughal M. R., et al. (2012). The homocysteine-inducible endoplasmic reticulum (ER) stress protein Herp counteracts mutant α-synuclein-induced ER stress via the homeostatic regulation of ER-resident calcium release channel proteins. Hum. Mol. Genet. 21 963–977. 10.1093/hmg/ddr502
    1. Bellucci A., Navarria L., Zaltieri M., Falarti E., Bodei S., Sigala S., et al. (2011). Induction of the unfolded protein response by α-synuclein in experimental models of Parkinson’s disease: α-Synuclein accumulation induces the UPR. J. Neurochem. 116 588–605. 10.1111/j.1471-4159.2010.07143.x
    1. Bendor J. T., Logan T. P., Edwards R. H. (2013). The Function of α-Synuclein. Neuron 79 1044–1066. 10.1016/j.neuron.2013.09.004
    1. Bertolotti A., Wang X., Novoa I., Jungreis R., Schlessinger K., Cho J. H., et al. (2001). Increased sensitivity to dextran sodium sulfate colitis in IRE1β-deficient mice. J. Clin. Invest. 107 585–593. 10.1172/jci11476
    1. Bertolotti A., Zhang Y., Hendershot L. M., Harding H. P., Ron D. (2000). Dynamic interaction of BiP and ER stress transducers in the unfolded-protein response. Nat. Cell Biol. 2 326–332. 10.1038/35014014
    1. Betzer C., Lassen L. B., Olsen A., Kofoed R. H., Reimer L., Gregersen E., et al. (2018). α-synuclein aggregates activate calcium pump SERCA leading to calcium dysregulation. EMBO Rep. 19:e44617. 10.15252/embr.201744617
    1. Bouman L., Schlierf A., Lutz A. K., Shan J., Deinlein A., Kast J., et al. (2011). Parkin is transcriptionally regulated by ATF4: evidence for an interconnection between mitochondrial stress and ER stress. Cell Death Differ. 18 769–782. 10.1038/cdd.2010.142
    1. Boyce M., Bryant K. F., Jousse C., Long K., Harding H. P., Scheuner D. (2005). A selective inhibitor of eIF2 dephosphorylation protects cells from ER stress. Science 307 935–939. 10.1126/science.1101902
    1. Braak H., Del Tredici K., Rüb U., de Vos R. A. I., Jansen Steur E. N. H., Braak E. (2003). Staging of brain pathology related to sporadic Parkinson’s disease. Neurobiol. Aging 24 197–211. 10.1016/s0197-4580(02)00065-9
    1. Breda C., Nugent M. L., Estranero J. G., Kyriacou C. P., Outeiro T. F., Steinert J. R., et al. (2015). Rab11 modulates α-synuclein-mediated defects in synaptic transmission and behaviour. Hum. Mol. Genet. 24 1077–1091. 10.1093/hmg/ddu521
    1. Burre J., Sharma M., Tsetsenis T., Buchman V., Etherton M. R., Sudhof T. C. (2010). α-synuclein promotes SNARE-complex assembly in vivo and in vitro. Science 329 1663–1667. 10.1126/science.1195227
    1. Buytaert E., Callewaert G., Hendrickx N., Scorrano L., Hartmann D., Missiaen L., et al. (2006). Role of endoplasmic reticulum depletion and multidomain proapoptotic BAX and BAK proteins in shaping cell death after hypericin-mediated photodynamic therapy. FASEB J. 20 756–758. 10.1096/fj.05-4305fje
    1. Chung C. Y., Khurana V., Auluck P. K., Tardiff D. F., Mazzulli J. R., Soldner F., et al. (2013). Identification and rescue of α-synuclein toxicity in Parkinson patient-derived neurons. Science 342 983–987. 10.1126/science.1245296
    1. Colla E., Coune P., Liu Y., Pletnikova O., Troncoso J. C., Iwatsubo T., et al. (2012a). Endoplasmic reticulum stress is important for the manifestations of α-synucleinopathy in vivo. J. Neurosci. 32 3306–3320. 10.1523/JNEUROSCI.5367-11.2012
    1. Colla E., Jensen P. H., Pletnikova O., Troncoso J. C., Glabe C., Lee M. K. (2012b). Accumulation of toxic -synuclein oligomer within endoplasmic reticulum occurs in -synucleinopathy in vivo. J. Neurosci. 32 3301–3305. 10.1523/JNEUROSCI.5368-11.2012
    1. Colla E., Panattoni G., Ricci A., Rizzi C., Rota L., Carucci N., et al. (2018). Toxic properties of microsome-associated α-synuclein species in mouse primary neurons. Neurobiol. Dis. 111 36–47. 10.1016/j.nbd.2017.12.004
    1. Conn K. J., Gao W., McKee A., Lan M. S., Ullman M. D., Eisenhauer P. B., et al. (2004). Identification of the protein disulfide isomerase family member PDIp in experimental Parkinson’s disease and Lewy body pathology. Brain Res. 1022 164–172. 10.1016/j.brainres.2004.07.026
    1. Connor J. H., Weiser D. C., Li S., Hallenbeck J. M., Shenolikar S. (2001). Growth Arrest and DNA Damage-Inducible Protein GADD34 Assembles a Novel Signaling Complex Containing Protein Phosphatase 1 and Inhibitor 1. Mol. Cell. Biol. 21 6841–6850. 10.1128/mcb.21.20.6841-6850.2001
    1. Cooper A. A., Gitler A. D., Cashikar A., Haynes C. M., Hill K. J., Bhullar B. (2006). α-synuclein blocks ER-Golgi traffic and rab1 rescues neuron loss in Parkinson’s models. Science 313 324–328. 10.1126/science.1129462
    1. Credle J. J., Finer-Moore J. S., Papa F. R., Stroud R. M., Walter P. (2005). On the mechanism of sensing unfolded protein in the endoplasmic reticulum. Proc. Natl. Acad. Sci. U.S.A. 102 18773–18784.
    1. Credle J. J., Forcelli P. A., Delannoy M., Oaks A. W., Permaul E., Berry D. L., et al. (2015). α-Synuclein-mediated inhibition of ATF6 processing into COPII vesicles disrupts UPR signaling in Parkinson’s disease. Neurobiol. Dis. 76 112–125. 10.1016/j.nbd.2015.02.005
    1. Cremades N., Cohen S. I. A., Deas E., Abramov A. Y., Chen A. Y., Orte A., et al. (2012). Direct observation of the interconversion of normal and toxic forms of α-synuclein. Cell 149 1048–1059. 10.1016/j.cell.2012.03.037
    1. Cullinan S. B., Diehl J. A. (2004). PERK-dependent activation of Nrf2 contributes to redox homeostasis and cell survival following endoplasmic reticulum stress. J. Biol. Chem. 279 20108–20117. 10.1074/jbc.m314219200
    1. Cullinan S. B., Diehl J. A. (2006). Coordination of ER and oxidative stress signaling: The PERK/Nrf2 signaling pathway. Int. J. Biochem. Cell Biol. 38 317–332. 10.1016/j.biocel.2005.09.018
    1. Deng J., Lu P. D., Zhang Y., Scheuner D., Kaufman R. J., Sonenberg N., et al. (2004). Translational repression mediates activation of nuclear factor kappa b by phosphorylated translation initiation factor 2. Mol. Cell. Biol. 24 10161–10168. 10.1128/mcb.24.23.10161-10168.2004
    1. Diao J., Burré J., Vivona S., Cipriano D. J., Sharma M., Kyoung M., et al. (2013). Native α-synuclein induces clustering of synaptic-vesicle mimics via binding to phospholipids and synaptobrevin-2/VAMP2. eLife 2:e00592. 10.7554/eLife.00592
    1. Duplan E., Giaime E., Viotti J., Sevalle J., Corti O., Brice A., et al. (2013). ER-stress-associated functional link between Parkin and DJ-1 via a transcriptional cascade involving the tumor suppressor p53 and the spliced X-box binding protein XBP-1. J. Cell Sci. 126 2124–2133. 10.1242/jcs.127340
    1. Egawa N., Yamamoto K., Inoue H., Hikawa R., Nishi K., Mori K., et al. (2011). The endoplasmic reticulum stress sensor, ATF6α, protects against neurotoxin-induced dopaminergic neuronal death. J. Biol. Chem. 286 7947–7957. 10.1074/jbc.M110.156430
    1. Feany M. B., Bender W. W. (2000). A Drosophila model of Parkinson’s disease. Nature 404 394–398.
    1. Galehdar Z., Swan P., Fuerth B., Callaghan S. M., Park D. S., Cregan S. P. (2010). Neuronal apoptosis induced by endoplasmic reticulum stress is regulated by ATF4-CHOP-mediated induction of the Bcl-2 homology 3-only member PUMA. J. Neurosci. 30 16938–16948. 10.1523/JNEUROSCI.1598-10.2010
    1. Gardner B. M., Walter P. (2011). Unfolded proteins are Ire1-activating ligands that directly induce the unfolded protein response. Science 333 1891–1894. 10.1126/science.1209126
    1. Ghosh A. P., Klocke B. J., Ballestas M. E., Roth K. A. (2012). CHOP potentially co-operates with FOXO3a in neuronal cells to regulate PUMA and BIM expression in response to ER stress. PLoS One 7:e39586. 10.1371/journal.pone.0039586
    1. Gitler A. D., Bevis B. J., Shorter J., Strathearn K. E., Hamamichi S., Su L. J., et al. (2008). The Parkinson’s disease protein α-synuclein disrupts cellular Rab homeostasis. Proc. Natl. Acad. Sci. U.S.A. 105 145–150. 10.1073/pnas.0710685105
    1. Goedert M., Spillantini M. G., Del Tredici K., Braak H. (2013). 100 years of Lewy pathology. Nat. Rev. Neurol. 9 13–24. 10.1038/nrneurol.2012.242
    1. Gorbatyuk M. S., Shabashvili A., Chen W., Meyers C., Sullivan L. F., Salganik M., et al. (2012). Glucose regulated protein 78 diminishes α-synuclein neurotoxicity in a rat model of Parkinson disease. Mol. Ther. 20 1327–1337. 10.1038/mt.2012.28
    1. Görlach A., Bertram K., Hudecova S., Krizanova O. (2015). Calcium and ROS: A mutual interplay. Redox Biol. 6 260–271. 10.1016/j.redox.2015.08.010
    1. Görlach A., Klappa P., Kietzmann T. (2006). The endoplasmic reticulum: folding, calcium homeostasis, signaling, and redox control. Antioxid. Redox Signal. 8 1391–1418. 10.1089/ars.2006.8.1391
    1. Han D., Lerner A. G., Vande Walle L., Upton J.-P., Xu W., Hagen A., et al. (2009). IRE1α kinase activation modes control alternate endoribonuclease outputs to determine divergent cell fates. Cell 138 562–575. 10.1016/j.cell.2009.07.017
    1. Harding H. P., Novoa I., Zhang Y., Zeng H., Wek R., Schapira M., et al. (2000a). Regulated translation initiation controls stress-induced gene expression in mammalian cells. Mol. Cell 6 1099–1108. 10.1016/s1097-2765(00)00108-8
    1. Harding H. P., Zhang Y., Bertolotti A., Zeng H., Ron D. (2000b). Perk is essential for translational regulation and cell survival during the unfolded protein response. Mol. Cell 5 897–904. 10.1016/s1097-2765(00)80330-5
    1. Harding H. P., Zhang Y., Ron D. (1999). Protein translation and folding are coupled by an endoplasmic-reticulum-resident kinase. Nature 397 271–274. 10.1038/16729
    1. Haze K., Yoshida H., Yanagi H., Yura T., Mori K. (1999). Mammalian transcription factor ATF6 is synthesized as a transmembrane protein and activated by proteolysis in response to endoplasmic reticulum stress. Mol. Biol. Cell 10 3787–3799. 10.1091/mbc.10.11.3787
    1. Heman-Ackah S. M., Manzano R., Hoozemans J. J., Scheper W., Flynn R., Haerty W., et al. (2017). α-synuclein induces the unfolded protein response in Parkinson’s disease SNCA triplication iPSC-derived neurons. Hum. Mol. Genet. 26 4441–4450. 10.1093/hmg/ddx331
    1. Hendershot L. M. (2004). The ER function BiP is a master regulator of ER function. Mt. Sinai J. Med. 71 289–297.
    1. Hetz C., Bernasconi P., Fisher J., Lee A.-H., Bassik M. C., Antonsson B., et al. (2006). Proapoptotic BAX and BAK modulate the unfolded protein response by a direct interaction with IRE1α. Science 312 572–576. 10.1126/science.1123480
    1. Hollien J., Lin J. H., Li H., Stevens N., Walter P., Weissman J. S. (2009). Regulated Ire1-dependent decay of messenger RNAs in mammalian cells. J. Cell Biol. 186 323–331. 10.1083/jcb.200903014
    1. Hollien J., Weissman J. S. (2006). Decay of endoplasmic reticulum-localized mRNAs during the unfolded protein response. Science 313 104–107. 10.1126/science.1129631
    1. Holmqvist S., Chutna O., Bousset L., Aldrin-Kirk P., Li W., Björklund T., et al. (2014). Direct evidence of Parkinson pathology spread from the gastrointestinal tract to the brain in rats. Acta Neuropathol. 128 805–820. 10.1007/s00401-014-1343-6
    1. Holtz W. A., O’Malley K. L. (2003). Parkinsonian mimetics induce aspects of unfolded protein response in death of dopaminergic neurons. J. Biol. Chem. 278 19367–19377. 10.1074/jbc.m211821200
    1. Hoozemans J. J. M., van Haastert E. S., Eikelenboom P., de Vos R. A. I., Rozemuller J. M., Scheper W. (2007). Activation of the unfolded protein response in Parkinson’s disease. Biochem. Biophys. Res. Commun. 354 707–711.
    1. Hu P., Han Z., Couvillon A. D., Kaufman R. J., Exton J. H. (2006). Autocrine tumor necrosis factor α links endoplasmic reticulum stress to the membrane death receptor pathway through IRE1 -mediated NF- B activation and down-regulation of TRAF2 expression. Mol. Cell. Biol. 26 3071–3084. 10.1128/mcb.26.8.3071-3084.2006
    1. Keestra-Gounder A. M., Byndloss M. X., Seyffert N., Young B. M., Chávez-Arroyo A., Tsai A. Y., et al. (2016). NOD1 and NOD2 signalling links ER stress with inflammation. Nature 532 394–397. 10.1038/nature17631
    1. Kimata Y., Ishiwata-Kimata Y., Ito T., Hirata A., Suzuki T., Oikawa D., et al. (2007). Two regulatory steps of ER-stress sensor Ire1 involving its cluster formation and interaction with unfolded proteins. J. Cell Biol. 179 75–86. 10.1083/jcb.200704166
    1. Klee M., Pallauf K., Alcalá S., Fleischer A., Pimentel-Muiños F. X. (2009). Mitochondrial apoptosis induced by BH3-only molecules in the exclusive presence of endoplasmic reticular Bak. EMBO J. 28 1757–1768. 10.1038/emboj.2009.90
    1. Lakso M., Vartiainen S., Moilanen A.-M., Sirviö J., Thomas J. H., Nass R., et al. (2003). Dopaminergic neuronal loss and motor deficits in Caenorhabditis elegans overexpressing human α-synuclein. J. Neurochem. 86 165–172. 10.1046/j.1471-4159.2003.01809.x
    1. Lashuel H. A., Petre B. M., Wall J., Simon M., Nowak R. J., Walz T., et al. (2002). α-synuclein, especially the Parkinson’s disease-associated mutants, forms pore-like annular and tubular protofibrils. J. Mol. Biol. 322 1089–1102. 10.1016/s0022-2836(02)00735-0
    1. Lee A.-H., Iwakoshi N. N., Glimcher L. H. (2003). XBP-1 regulates a subset of endoplasmic reticulum resident chaperone genes in the unfolded protein response. Mol. Cell. Biol. 23 7448–7459. 10.1128/mcb.23.21.7448-7459.2003
    1. Lee M. K., Stirling W., Xu Y., Xu X., Qui D., Mandir A. S., et al. (2002). Human α-synuclein-harboring familial Parkinson’s disease-linked Ala-53 –> Thr mutation causes neurodegenerative disease with α-synuclein aggregation in transgenic mice. Proc. Natl. Acad. Sci. U.S.A. 99 8968–8973. 10.1073/pnas.132197599
    1. Li T., Su L., Lei Y., Liu X., Zhang Y., Liu X. (2015). DDIT3 and KAT2A proteins regulate TNFRSF10A and TNFRSF10B expression in endoplasmic reticulum stress-mediated apoptosis in human lung cancer cells. J. Biol. Chem. 290 11108–11118. 10.1074/jbc.M115.645333
    1. Lin J. H., Li H., Yasumura D., Cohen H. R., Zhang C., Panning B., et al. (2007). IRE1 signaling affects cell fate during the unfolded protein response. Science 318 944–949. 10.1126/science.1146361
    1. Lu M., Lawrence D. A., Marsters S., Acosta-Alvear D., Kimmig P., Mendez A. S., et al. (2014). Opposing unfolded-protein-response signals converge on death receptor 5 to control apoptosis. Science 345 98–101. 10.1126/science.1254312
    1. Luk K. C., Kehm V., Carroll J., Zhang B., O’Brien P., Trojanowski J. Q., et al. (2012). Pathological α-synuclein transmission initiates Parkinson-like neurodegeneration in nontransgenic mice. Science 338 949–953. 10.1126/science.1227157
    1. Ma K., Vattem K. M., Wek R. C. (2002). Dimerization and release of molecular chaperone inhibition facilitate activation of eukaryotic initiation factor-2 kinase in response to endoplasmic reticulum stress. J. Biol. Chem. 277 18728–18735. 10.1074/jbc.m200903200
    1. Marciniak S. J. (2004). CHOP induces death by promoting protein synthesis and oxidation in the stressed endoplasmic reticulum. Genes Dev. 18 3066–3077. 10.1101/gad.1250704
    1. Martínez G., Vidal R. L., Mardones P., Serrano F. G., Ardiles A. O., Wirth C., et al. (2016). Regulation of memory formation by the transcription factor XBP1. Cell Rep. 14 1382–1394. 10.1016/j.celrep.2016.01.028
    1. Martinon F., Chen X., Lee A.-H., Glimcher L. H. (2010). TLR activation of the transcription factor XBP1 regulates innate immune responses in macrophages. Nat. Immunol. 11 411–418. 10.1038/ni.1857
    1. Martín-Pérez R., Niwa M., López-Rivas A. (2012). ER stress sensitizes cells to TRAIL through down-regulation of FLIP and Mcl-1 and PERK-dependent up-regulation of TRAIL-R2. Apoptosis 17 349–363. 10.1007/s10495-011-0673-2
    1. Masliah E. (2000). Dopaminergic loss and inclusion body formation in α-synuclein mice: implications for neurodegenerative disorders. Science 287 1265–1269. 10.1126/science.287.5456.1265
    1. Masuda-Suzukake M., Nonaka T., Hosokawa M., Oikawa T., Arai T., Akiyama H., et al. (2013). Prion-like spreading of pathological α-synuclein in brain. Brain 136 1128–1138. 10.1093/brain/awt037
    1. Mazzulli J. R., Zunke F., Isacson O., Studer L., Krainc D. (2016). α-Synuclein–induced lysosomal dysfunction occurs through disruptions in protein trafficking in human midbrain synucleinopathy models. Proc. Natl. Acad. Sci. U.S.A. 113 1931–1936. 10.1073/pnas.1520335113
    1. Nakagawa T., Zhu H., Morishima N., Li E., Xu J., Yankner B. A., et al. (2000). Caspase-12 mediates endoplasmic-reticulum-specific apoptosis and cytotoxicity by amyloid-β. Nature 403 98–103. 10.1038/47513
    1. Nemani V. M., Lu W., Berge V., Nakamura K., Onoa B., Lee M. K., et al. (2010). Increased expression of α-synuclein reduces neurotransmitter release by inhibiting synaptic vesicle reclustering after endocytosis. Neuron 65 66–79. 10.1016/j.neuron.2009.12.023
    1. Nishitoh H., Matsuzawa A., Tobiume K., Saegusa K., Takeda K., Inoue K. (2002). ASK1 is essential for endoplasmic reticulum stress-induced neuronal cell death triggered by expanded polyglutamine repeats. Genes Dev. 16 1345–1355. 10.1101/gad.992302
    1. Novoa I., Zeng H., Harding H. P., Ron D. (2001). Feedback inhibition of the unfolded protein response by GADD34-mediated dephosphorylation of eIF2α. J. Cell Biol. 153 1011–1022. 10.1083/jcb.153.5.1011
    1. Obeng E. A., Boise L. H. (2005). Caspase-12 and caspase-4 are not required for caspase-dependent endoplasmic reticulum stress-induced apoptosis. J. Biol. Chem. 280 29578–29587. 10.1074/jbc.m502685200
    1. Puthalakath H., O’Reilly L. A., Gunn P., Lee L., Kelly P. N., Huntington N. D., et al. (2007). ER stress triggers apoptosis by activating BH3-only protein bim. Cell 129 1337–1349. 10.1016/j.cell.2007.04.027
    1. Qiu Q., Zheng Z., Chang L., Zhao Y.-S., Tan C., Dandekar A., et al. (2013). Toll-like receptor-mediated IRE1α activation as a therapeutic target for inflammatory arthritis. EMBO J. 32 2477–2490. 10.1038/emboj.2013.183
    1. Ray A., Zhang S., Rentas C., Caldwell K. A., Caldwell G. A. (2014). RTCB-1 mediates neuroprotection via XBP-1 mRNA splicing in the unfolded protein response pathway. J. Neurosci. 34 16076–16085. 10.1523/JNEUROSCI.1945-14.2014
    1. Recasens A., Dehay B., Bové J., Carballo-Carbajal I., Dovero S., Pérez-Villalba A., et al. (2014). Lewy body extracts from Parkinson disease brains trigger α-synuclein pathology and neurodegeneration in mice and monkeys: LB-Induced Pathology. Ann. Neurol. 75 351–362. 10.1002/ana.24066
    1. Rey N. L., Petit G. H., Bousset L., Melki R., Brundin P. (2013). Transfer of human α-synuclein from the olfactory bulb to interconnected brain regions in mice. Acta Neuropathol. 126 555–573. 10.1007/s00401-013-1160-3
    1. Ryu E. J., Harding H. P., Angelastro J. M., Vitolo O. V., Ron D., Greene L. A. (2002). Endoplasmic reticulum stress and the unfolded protein response in cellular models of Parkinson’s disease. J. Neurosci. 22 10690–10698.
    1. Sacino A. N., Brooks M., Thomas M. A., McKinney A. B., Lee S., Regenhardt R. W., et al. (2014). Intramuscular injection of α-synuclein induces CNS α-synuclein pathology and a rapid-onset motor phenotype in transgenic mice. Proc. Natl. Acad. Sci. U.S.A. 111 10732–10737. 10.1073/pnas.1321785111
    1. Sado M., Yamasaki Y., Iwanaga T., Onaka Y., Ibuki T., Nishihara S., et al. (2009). Protective effect against Parkinson’s disease-related insults through the activation of XBP1. Brain Res. 1257 16–24. 10.1016/j.brainres.2008.11.104
    1. Saleh M., Mathison J. C., Wolinski M. K., Bensinger S. J., Fitzgerald P., Droin N., et al. (2006). Enhanced bacterial clearance and sepsis resistance in caspase-12-deficient mice. Nature 440 1064–1068. 10.1038/nature04656
    1. Scheuner D., Song B., McEwen E., Liu C., Laybutt R., Gillespie P., et al. (2001). Translational control is required for the unfolded protein response and in vivo glucose homeostasis. Mol. Cell 7 1165–1176. 10.1016/s1097-2765(01)00265-9
    1. Schindler A. J., Schekman R. (2009). In vitro reconstitution of ER-stress induced ATF6 transport in COPII vesicles. Proc. Natl. Acad. Sci. U.S.A. 106 17775–17780. 10.1073/pnas.0910342106
    1. Scorrano L., Oakes S. A., Opferman J. T., Cheng E. H., Sorcinelli M. D., Pozzan T. (2003). BAX and BAK regulation of endoplasmic reticulum Ca2+: a control point for apoptosis. Science 300 135–139. 10.1126/science.1081208
    1. Selvaraj S., Sun Y., Watt J. A., Wang S., Lei S., Birnbaumer L., et al. (2012). Neurotoxin-induced ER stress in mouse dopaminergic neurons involves downregulation of TRPC1 and inhibition of AKT/mTOR signaling. J. Clin. Invest. 122 1354–1367. 10.1172/JCI61332
    1. Shen J., Snapp E. L., Lippincott-Schwartz J., Prywes R. (2005). Stable binding of ATF6 to BiP in the endoplasmic reticulum stress response. Mol. Cell. Biol. 25 921–932. 10.1128/mcb.25.3.921-932.2005
    1. Shenderov K., Riteau N., Yip R., Mayer-Barber K. D., Oland S., Hieny S., et al. (2014). Cutting edge: endoplasmic reticulum stress licenses macrophages to produce mature IL-1 in response to TLR4 stimulation through a caspase-8- and TRIF-dependent pathway. J. Immunol. 192 2029–2033. 10.4049/jimmunol.1302549
    1. Shi Y., Vattem K. M., Sood R., An J., Liang J., Stramm L., et al. (1998). Identification and characterization of pancreatic eukaryotic initiation factor 2 α-subunit kinase, PEK, involved in translational control. Mol. Cell. Biol. 18 7499–7509. 10.1128/mcb.18.12.7499
    1. Silva R. M., Ries V., Oo T. F., Yarygina O., Jackson-Lewis V., Ryu E. J., et al. (2005). CHOP/GADD153 is a mediator of apoptotic death in substantia nigra dopamine neurons in an in vivo neurotoxin model of parkinsonism. J. Neurochem. 95 974–986. 10.1111/j.1471-4159.2005.03428.x
    1. Smith J. A., Khan M., Magnani D. D., Harms J. S., Durward M., Radhakrishnan G. K., et al. (2013). Brucella induces an unfolded protein response via TcpB that supports intracellular replication in macrophages. PLoS Pathog. 9:e1003785. 10.1371/journal.ppat.1003785
    1. Smith M. H., Ploegh H. L., Weissman J. S. (2011). Road to ruin: targeting proteins for degradation in the endoplasmic reticulum. Science 334 1086–1090. 10.1126/science.1209235
    1. Smith W. W., Jiang H., Pei Z., Tanaka Y., Morita H., Sawa A., et al. (2005). Endoplasmic reticulum stress and mitochondrial cell death pathways mediate A53T mutant α-synuclein-induced toxicity. Hum. Mol. Genet. 14 3801–3811. 10.1093/hmg/ddi396
    1. Song J., Kim B. C., Nguyen D.-T. T., Samidurai M., Choi S.-M. (2017). Levodopa (L-DOPA) attenuates endoplasmic reticulum stress response and cell death signaling through DRD2 in SH-SY5Y neuronal cells under α-synuclein-induced toxicity. Neuroscience 358 336–348. 10.1016/j.neuroscience.2017.06.060
    1. Starck S. R., Tsai J. C., Chen K., Shodiya M., Wang L., Yahiro K., et al. (2016). Translation from the 5’ untranslated region shapes the integrated stress response. Science 351:aad3867. 10.1126/science.aad3867
    1. Sun X., Liu J., Crary J. F., Malagelada C., Sulzer D., Greene L. A., et al. (2013). ATF4 protects against neuronal death in cellular parkinson’s disease models by maintaining levels of Parkin. J. Neurosci. 33 2398–2407. 10.1523/jneurosci.2292-12.2013
    1. Trinh M. A., Klann E. (2013). Translational control by eIF2α kinases in long-lasting synaptic plasticity and long-term memory. Neurobiol. Learn. Mem. 105 93–99. 10.1016/j.nlm.2013.04.013
    1. Tsuru A., Fujimoto N., Takahashi S., Saito M., Nakamura D., Iwano M., et al. (2013). Negative feedback by IRE1 optimizes mucin production in goblet cells. Proc. Natl. Acad. Sci. U.S.A. 110 2864–2869. 10.1073/pnas.1212484110
    1. Tsuru A., Imai Y., Saito M., Kohno K. (2016). Novel mechanism of enhancing IRE1α-XBP1 signalling via the PERK-ATF4 pathway. Sci. Rep. 6:24217. 10.1038/srep24217
    1. Tuttle M. D., Comellas G., Nieuwkoop A. J., Covell D. J., Berthold D. A., Kloepper K. D., et al. (2016). Solid-state NMR structure of a pathogenic fibril of full-length human α-synuclein. Nat. Struct. Mol. Biol. 23 409–415. 10.1038/nsmb.3194
    1. Upton J.-P., Wang L., Han D., Wang E. S., Huskey N. E., Lim L., et al. (2012). IRE1 cleaves select microRNAs during ER stress to derepress translation of proapoptotic caspase-2. Science 338 818–822. 10.1126/science.1226191
    1. Urano F., Wang X., Bertolotti A., Zhang Y., Chung P., Harding H. P., et al. (2000). Coupling of stress in the ER to activation of JNK protein kinases by transmembrane protein kinase IRE1. Science 287 664–666. 10.1126/science.287.5453.664
    1. Valdes P., Mercado G., Vidal R. L., Molina C., Parsons G., Court F. A., et al. (2014). Control of dopaminergic neuron survival by the unfolded protein response transcription factor XBP1. Proc. Natl. Acad. Sci. U.S.A. 111 6804–6809. 10.1073/pnas.1321845111
    1. Vattem K. M., Wek R. C. (2004). Reinitiation involving upstream ORFs regulates ATF4 mRNA translation in mammalian cells. Proc. Natl. Acad. Sci. U.S.A. 101 11269–11274. 10.1073/pnas.0400541101
    1. Volpicelli-Daley L. A., Luk K. C., Lee V. M.-Y. (2014). Addition of exogenous α-synuclein preformed fibrils to primary neuronal cultures to seed recruitment of endogenous α-synuclein to Lewy body and Lewy neurite–like aggregates. Nat. Protoc. 9 2135–2146. 10.1038/nprot.2014.143
    1. Walter P., Ron D. (2011). The unfolded protein response: from stress pathway to homeostatic regulation. Science 334 1081–1086. 10.1126/science.1209038
    1. Wang L., Das U., Scott D. A., Tang Y., McLean P. J., Roy S. (2014). α-Synuclein multimers cluster synaptic vesicles and attenuate recycling. Curr. Biol. 24 2319–2326. 10.1016/j.cub.2014.08.027
    1. Wang X.-Z., Harding H. P., Zhang Y., Jolicoeur E. M., Kuroda M., Ron D. (1998). Cloning of mammalian Ire1 reveals diversity in the ER stress responses. EMBO J. 17 5708–5717. 10.1093/emboj/17.19.5708
    1. Yoneda T., Imaizumi K., Oono K., Yui D., Gomi F., Katayama T., et al. (2001). Activation of caspase-12, an endoplastic reticulum (ER) resident caspase, through tumor necrosis factor receptor-associated factor 2-dependent mechanism in response to the ER stress. J. Biol. Chem. 276 13935–13940. 10.1074/jbc.m010677200
    1. Yoshida H., Matsui T., Yamamoto A., Okada T., Mori K. (2001). XBP1 mRNA is induced by ATF6 and spliced by IRE1 in response to ER stress to produce a highly active transcription factor. Cell 107 881–891. 10.1016/s0092-8674(01)00611-0
    1. Yoshida H., Okada T., Haze K., Yanagi H., Yura T., Negishi M., et al. (2000). ATF6 activated by proteolysis binds in the presence of NF-Y (CBF) directly to the cis-acting element responsible for the mammalian unfolded protein response. Mol. Cell. Biol. 20 6755–6767. 10.1128/mcb.20.18.6755-6767.2000
    1. Yuan Y., Cao P., Smith M. A., Kramp K., Huang Y., Hisamoto N., et al. (2011). Dysregulated LRRK2 signaling in response to endoplasmic reticulum stress leads to dopaminergic neuron degeneration in C. elegans. PLoS One 6:e22354. 10.1371/journal.pone.0022354
    1. Zong W.-X., Li C., Hatzivassiliou G., Lindsten T., Yu Q.-C., Yuan J., et al. (2003). Bax and Bak can localize to the endoplasmic reticulum to initiate apoptosis. J. Cell Biol. 162 59–69. 10.1083/jcb.200302084

Source: PubMed

Sponzoři a spolupracovníci

Zdravotní podmínky

Drogové intervence

3
Předplatit