The Endoplasmic Reticulum Unfolded Protein Response in Neurodegenerative Disorders and Its Potential Therapeutic Significance

Abisambra, 2013, Tau accumulation activates the unfolded protein response by impairing endoplasmic reticulum-associated degradation., J. Neurosci., 33, 9498, 10.1523/JNEUROSCI.5397-12.2013

Acosta-Alvear, 2007, XBP1 controls diverse cell type- and condition-specific transcriptional regulatory networks., Mol. Cell, 27, 53, 10.1016/j.molcel.2007.06.011

Adolph, 2013, Paneth cells as a site of origin for intestinal inflammation., Nature, 503, 272, 10.1038/nature12599

Aghajani, 2006, A point mutation at the calreticulin gene core promoter conserved sequence in a case of schizophrenia., Am. J. Med. Genet. B Neuropsychiatr. Genet., 294, 10.1002/ajmg.b.30300

Al-Saif, 2011, A mutation in sigma-1 receptor causes juvenile amyotrophic lateral sclerosis., Ann. Neurol., 70, 913, 10.1002/ana.22534

Amodio, 2011, Proteomic signatures in thapsigargin-treated hepatoma cells., Chem. Res. Toxicol., 24, 1215, 10.1021/tx200109y

Amodio, 2009, Endoplasmic Reticulum stress reduces the export from the ER and alters the architecture of post-ER compartments., Int. J. Biochem. Cell Biol., 41, 2511, 10.1016/j.biocel.2009.08.006

Amodio, 2016, Remondelli P. Identification of a microRNA (miR-663a) induced by ER stress and its target gene PLOD3 by a combined microRNome and proteome approach., Cell Biol. Toxicol., 32, 285, 10.1007/s10565-016-9335-z

Amodio, 2013, Endoplasmic reticulum stress reduces COPII vesicle formation and modifies Sec23a cycling at ERESs., FEBS Lett., 587, 3261, 10.1016/j.febslet.2013.08.021

Andersen, 2011, Clinical genetics of amyotrophic lateral sclerosis: what do we really know?, Nat. Rev. Neurol., 7, 603, 10.1038/nrneurol.2011.150

Arrasate, 2012, Protein aggregates in Huntington’s disease., Exp. Neurol., 238, 1, 10.1016/j.expneurol.2011.12.013

Atkin, 2006, Induction of the unfolded protein response in familial amyotrophic lateral sclerosis and association of protein-disulfide isomerase with superoxide dismutase 1., J. Biol. Chem., 281, 30152, 10.1074/jbc.M603393200

Balch, 2008, Adapting proteostasis for disease intervention., Science, 319, 916, 10.1126/science.1141448

B’Chir, 2013, The eIF2alpha/ATF4 pathway is essential for stress-induced autophagy gene expression., Nucleic Acids Res., 41, 7683, 10.1093/nar/gkt563

Belal, 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, 10.1093/hmg/ddr502

Bellucci, 2011, Induction of the unfolded protein response by α-synuclein in experimental models of Parkinson’s disease., J. Neurochem., 116, 588, 10.1111/j.1471-4159.2010.07143.x

Berridge, 2003, Calcium signalling: dynamics, homeostasis and remodeling., Nat. Rev. Mol. Cell Biol., 4, 517, 10.1038/nrm1155

Blais, 2004, Activating transcription factor 4 is translationally regulated by hypoxic stress., Mol. Cell. Biol., 24, 7469, 10.1128/MCB.24.17.7469-7482.2004

Bouman, 2011, Parkin is transcriptionally regulated by ATF4: evidence for an interconnection between mitochondrial stress and ER stress., Cell Death Differ., 18, 769, 10.1038/cdd.2010.142

Bruch, 2015, Early Neurodegeneration in the Brain of a Child Without Functional PKR-like Endoplasmic Reticulum Kinase., J. Neuropathol. Exp. Neurol., 74, 850, 10.1097/NEN.0000000000000224

Calfon, 2002, IRE1 couples endoplasmic reticulum load to secretory capacity by processing the XBP-1 mRNA., Nature, 415, 92, 10.1038/415092a

Casas-Tinto, 2011, The ER stress factor XBP1s prevents amyloid-beta neurotoxicity., Hum. Mol. Genet., 20, 2144, 10.1093/hmg/ddr100

Celardo, 2016, Mitofusin-mediated ER stress triggers neurodegeneration in pink1/parkin models of Parkinson’s disease., Cell Death Dis., 7, 10.1038/cddis.2016.173

Chen, 2012, Autophagy dysregulation in amyotrophic lateral sclerosis., Brain Pathol., 22, 110, 10.1111/j.1750-3639.2011.00546.x

Chen, 2011, Dantrolene is neuroprotective in Huntington’s disease transgenic mouse model., Mol. Neurodegener., 6, 10.1186/1750-1326-6-81

Cheroni, 2009, Functional alterations of the ubiquitin-proteasome system in motor neurons of a mouse model of familial amyotrophic lateral sclerosis., Hum. Mol. Genet., 18, 82, 10.1093/hmg/ddn319

Chung, 2016, Parkin and PINK1 Patient iPSC-derived midbrain dopamine neurons exhibit mitochondrial dysfunction and alpha-synuclein accumulation., Stem Cell Rep., 7, 664, 10.1016/j.stemcr.2016.08.012

Clapham, 2007, Calcium signaling., Cell, 13, 1047, 10.1016/j.cell.2007.11.028

Colla, , Endoplasmic reticulum stress is important for the manifestations of α-synucleinopathy in vivo., J. Neurosci., 32, 3306, 10.1523/JNEUROSCI.5367-11.2012

Colla, , Accumulation of toxic α-synuclein oligomer within endoplasmic reticulum occurs in α-synucleinopathy in vivo., J. Neurosci., 32, 3301, 10.1523/JNEUROSCI.5368-11.2012

Cooper, 2006, α-synuclein blocks ER-Golgi traffic and Rab1 rescues neuron loss in Parkinson’s models., Science, 313, 324, 10.1126/science.1129462

Cullinan, 2003, Nrf2 is a direct PERK substrate and effector of PERK-dependent cell survival., Mol. Cell. Biol., 23, 7198, 10.1128/MCB.23.20.7198-7209.2003

Dafinca, 2016, C9orf72 hexanucleotide expansions are associated with altered endoplasmic reticulum calcium homeostasis, and stress granule formation in induced pluripotent stem cell-derived neurons from patients with amyotrophic lateral sclerosis, and frontotemporal dementia., Stem Cells, 34, 2063, 10.1002/stem.2388

Das, 2015, Preventing proteostasis diseases by selective inhibition of a phosphatase regulatory subunit., Science, 348, 239, 10.1126/science.aaa4484

DeJesus-Hernandez, 2011, Expanded GGGGCC hexanucleotide repeat in noncoding region of C9ORF72 causes chromosome 9p-linked FTD and ALS., Neuron, 72, 245, 10.1016/j.neuron.2011.09.011

del Toro, 2006, Mutant huntingtin impairs the post-Golgi trafficking of brain-derived neurotrophic factor but not its Val66Met polymorphism., J. Neurosci., 26, 12748, 10.1523/JNEUROSCI.3873-06.2006

Deng, 2011, Mutations in UBQLN2 cause dominant X-linked juvenile and adult-onset ALS and ALS/dementia., Nature, 477, 211, 10.1038/nature10353

Devi, 2013, Deletion of the eIF2α Kinase GCN2 fails to rescue the memory decline associated with Alzheimer’s disease., PLoS ONE, 8, 10.1371/journal.pone.0077335

Domingues, 2007, Altered subcellular distribution of the Alzheimer’s amyloid precursor protein under stress conditions., Ann. N. Y. Acad. Sci, 1096, 184, 10.1196/annals.1397.085

Duennwald, 2008, Impaired ERAD and ER stress are early and specific events in polyglutamine toxicity., Genes Dev., 22, 3308, 10.1101/gad.1673408

Duplan, 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, 10.1242/jcs.127340

Duran-Aniotz, 2017, IRE1 signaling exacerbates Alzheimer’s disease pathogenesis., Acta Neuropathol., 10.1007/s00401-017-1694-x

Egawa, 2011, The endoplasmic reticulum stress sensor, ATF6α, protects against neurotoxin-induced dopaminergic neuronal death., J. Biol. Chem., 286, 7947, 10.1074/jbc.M110.156430

Erpapazoglou, 2017, From dysfunctional endoplasmic reticulum-mitochondria coupling to neurodegeneration., Neurochem. Int., 10.1016/j.neuint.2017.03.021

Farg, 2012, Mutant FUS induces endoplasmic reticulum stress in amyotrophic lateral sclerosis and interacts with protein disulfide-isomerase., Neurobiol. Aging, 33, 2855, 10.1016/j.neurobiolaging.2012.02.009

Farg, 2014, C9ORF72, implicated in amytrophic lateral sclerosis and frontotemporal dementia, regulates endosomal trafficking., Hum. Mol. Genet., 23, 3579, 10.1093/hmg/ddu068

Fasana, 2010, A VAPB mutant linked to amyotrophic lateral sclerosis generates a novel form of organized smooth endoplasmic reticulum., FASEB J., 24, 1419, 10.1096/fj.09-147850

Fecto, 2011, Making connections: pathology and genetics link amyotrophic lateral sclerosis with frontotemporal lobe dementia., J. Mol. Neurosci., 45, 663, 10.1007/s12031-011-9637-9

Fernandes, 2016, ER stress and autophagic perturbations lead to elevated extracellular alpha-Synuclein in GBA-N370S Parkinson’s iPSC-Derived Dopamine Neurons., Stem Cell Rep., 6, 342, 10.1016/j.stemcr.2016.01.013

Fernandez-Fernandez, 2011, Impaired ATF6α processing, decreased Rheb and neuronal cell cycle re-entry in Huntington’s disease., Neurobiol. Dis., 41, 23, 10.1016/j.nbd.2010.08.014

Fouillet, 2012, ER stress inhibits neuronal death by promoting autophagy., Autophagy, 8, 915, 10.4161/auto.19716

Fu, 2015, Phenotypic assays identify azoramide as a small-molecule modulator of the unfolded protein response with antidiabetic activity., Sci. Transl. Med., 7, 10.1126/scitranslmed.aaa9134

Gitler, 2008, The Parkinson’s disease protein α-synuclein disrupts cellular Rab homeostasis., Proc. Natl. Acad. Sci. U.S.A., 105, 145, 10.1073/pnas.0710685105

Gkogkas, 2008, VAPB interacts with and modulates the activity of ATF6., Hum. Mol. Genet., 17, 1517, 10.1093/hmg/ddn040

Goedert, 2010, The propagation of prion-like protein inclusions in neurodegenerative diseases., Trends Neurosci., 33, 317, 10.1016/j.tins.2010.04.003

Gorbatyuk, 2012, Glucose regulated protein 78 diminishes α-synuclein neurotoxicity in a rat model of Parkinson disease., Mol. Ther., 20, 1327, 10.1038/mt.2012.28

Green, 2014, To be or not to be? How selective autophagy and cell death govern cell fate., Cell, 157, 65, 10.1016/j.cell.2014.02.049

Gully, 2016, Up-regulation of activating transcription factor 4 induces severe loss of dopamine nigral neurons in a rat model of Parkinson’s disease., Neurosci. Lett., 627, 36, 10.1016/j.neulet.2016.05.039

Haass, 2007, Soluble protein oligomers in neurodegeneration: lessons from the Alzheimer’s amyloid β-peptide., Nat. Rev. Mol. Cell Biol., 8, 101, 10.1038/nrm2101

Halliday, 2015, Partial restoration of protein synthesis rates by the small molecule ISRIB prevents neurodegeneration without pancreatic toxicity., Cell Death Dis., 6, 10.1038/cddis.2015.49

Halliday, 2017, Repurposed drugs targeting eIF2α-P-mediated translational repression prevent neurodegeneration in mice., Brain, 140, 1768, 10.1093/brain/awx074

Harding, 1999, Protein translation and folding are coupled by an endoplasmic-reticulum-resident kinase., Nature, 397, 271, 10.1038/16729

Hartl, 2011, Molecular chaperones in protein folding and proteostasis., Nature, 475, 324, 10.1038/nature10317

Hashida, 2012, ATF6α promotes astroglial activation and neuronal survival in a chronic mouse model of Parkinson’s disease., PLoS ONE, 7, 10.1371/journal.pone.0047950

Haze, 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, 10.1091/mbc.10.11.3787

Hetz, 2012, The unfolded protein response: controlling cell fate decisions under ER stress and beyond., Nat. Rev. Mol. Cell Biol., 13, 89, 10.1038/nrm3270

Hetz, 2013, Targeting the unfolded protein response in disease., Nat. Rev. Drug Discov., 12, 703, 10.1038/nrd3976

Hetz, 2008, Unfolded protein response transcription factor XBP-1 does not influence prion replication or pathogenesis., Proc. Natl. Acad. Sci. U.S.A., 105, 757, 10.1073/pnas.0711094105

Hetz, 2011, The unfolded protein response: integrating stress signals through the stress sensor IRE1α., Physiol. Rev., 91, 1219, 10.1152/physrev.00001.2011

Hetz, 2014, Disturbance of endoplasmic reticulum proteostasis in neurodegenerative diseases., Nat. Rev. Neurosci., 15, 233, 10.1038/nrn3689

Hetz, 2007, The proapoptotic BCL-2 family member BIM mediates motoneuron loss in a model of amyotrophic lateral sclerosis., Cell Death Differ., 14, 1386, 10.1038/sj.cdd.4402166

Hetz, 2009, XBP-1 deficiency in the nervous system protects against amyotrophic lateral sclerosis by increasing autophagy., Genes Dev., 23, 2294, 10.1101/gad.1830709

Higo, 2010, Mechanism of ER stress-induced brain damage by IP3 receptor., Neuron, 68, 865, 10.1016/j.neuron.2010.11.010

Hong, 2016, Progesterone exerts neuroprotective effects against Aβ-induced neuroinflammation by attenuating ER stress in astrocytes., Int. Immunopharmacol., 33, 83, 10.1016/j.intimp.2016.02.002

Huang, 2017, Blockade of RyRs in the ER Attenuates 6-OHDA-induced calcium overload, cellular hypo-excitability and apoptosis in dopaminergic neurons., Front. Cell Neurosci., 11, 10.3389/fncel.2017.00052

Iwawaki, 2001, Translational control by the ER transmembrane kinase/ribonuclease IRE1 under ER stress., Nat. Cell Biol., 3, 158, 10.1038/35055065

Kakiuchi, 2007, Association analysis of HSP90B1 with bipolar disorder., J. Hum. Genet., 52, 794, 10.1007/s10038-007-0188-4

Kakiuchi, 2003, Impaired feedback regulation of XBP1 as a genetic risk factor for bipolar disorder., Nat. Genet., 35, 171, 10.1038/ng1235

Kanekura, 2006, Characterization of amyotrophic lateral sclerosis-linked P56S mutation of vesicle-associated membrane protein-associated protein B (VAPB/ALS8)., J. Biol. Chem., 281, 30223, 10.1074/jbc.M605049200

Katayama, 1999, Presinilin-1 mutations downregulate the signalling pathway of the unfolded-protein response., Nat. Cell Biol., 1, 479, 10.1038/70265

Kikuchi, 2006, Spinal cord endoplasmic reticulum stress associated with a microsomal accumulation of mutant superoxide dismutase-1 in an ALS model., Proc. Natl. Acad. Sci. U.S.A., 103, 6025, 10.1073/pnas.0509227103

Knowles, 2014, The amyloid state and its association with protein misfolding diseases., Nat. Rev. Mol. Cell Biol., 15, 384, 10.1038/nrm3810

Kouroku, 2007, ER stress (PERK/eIF2alpha phosphorylation) mediates the polyglutamine-induced LC3 conversion, an essential step for autophagy formation., Cell Death Differ., 14, 230, 10.1038/sj.cdd.4401984

Krantic, 2005, Molecular basis of programmed cell death involved in neurodegeneration., Trends Neurosci., 28, 670, 10.1016/j.tins.2005.09.011

Krols, 2016, Mitochondria-associated membranes as hubs for neurodegeneration., Acta Neuropathol., 131, 505, 10.1007/s00401-015-1528-7

Kudo, 2008, A molecular chaperone inducer protects neurons from ER stress., Cell Death Differ., 15, 364, 10.1038/sj.cdd.4402276

Kuijpers, 2013, The ALS8 protein VAPB interacts with the ER–Golgi recycling protein YIF1A and regulates membrane delivery into dendrites., EMBO J., 32, 2056, 10.1038/emboj.2013.131

Kwok, 2013, Association studies indicate that protein disulfide isomerase is a risk factor in amyotrophic lateral sclerosis., Free Radic. Biol. Med., 58, 81, 10.1016/j.freeradbiomed.2013.01.001

Lee, 2016, ENC1 modulates the aggregation and neurotoxicity of mutant huntingtin through p62 Under ER stress., Mol. Neurobiol., 53, 6620, 10.1007/s12035-015-9557-8

Lee, 2010, Lysosomal proteolysis and autophagy require presenilin 1 and are disrupted by Alzheimer-related PS1 mutations., Cell, 141, 1146, 10.1016/j.cell.2010.05.008

Lee, 2016, Activation of HIPK2 promotes ER stress-mediated neurodegeneration in amyotrophic lateral sclerosis., Neuron, 91, 41, 10.1016/j.neuron.2016.05.021

Lindquist, 2011, Chemical and biological approaches for adapting proteostasis to ameliorate protein misfolding and aggregation diseases: progress and prognosis., Cold Spring Harb. Perspect. Biol., 3, 10.1101/cshperspect.a004507

Liu, 2013, Polymorphism -116C/G of human X-box-binding protein 1 promoter is associated with risk of Alzheimer’s disease., CNS Neurosci. Ther., 19, 229, 10.1111/cns.12064

Liu, 2009, Preventing oxidative stress: a new role for XBP1., Cell Death. Differ., 16, 847, 10.1038/cdd.2009.14

Lourenco, 2013, TNF -α mediates PKR-dependent memory impairment and brain IRS-1 inhibition induced by Alzheimer’s β-amyloid oligomers in mice and monkeys., Cell Metab., 18, 831, 10.1016/j.cmet.2013.11.002

Luty, 2010, Sigma nonopioid intracellular receptor 1 mutations cause frontotemporal lobar degeneration-motor neuron disease., Ann. Neurol., 68, 639, 10.1002/ana.22274

Ma, 2013, Suppression of eIF2α kinases alleviates Alzheimer’s disease-related plasticity and memory deficits., Nat. Neurosci., 16, 1299, 10.1038/nn.3486

Makioka, 2010, Involvement of endoplasmic reticulum stress defined by activated unfolded protein response in multiple system atrophy., J. Neurol. Sci., 297, 60, 10.1016/j.jns.2010.06.019

Martin, 2011, Recent advances in the genetics of Parkinson’s disease., Annu. Rev. Genomics Hum. Genet., 12, 301, 10.1146/annurev-genom-082410-101440

Matus, 2012, Hormesis: protecting neurons against cellular stress in Parkinson disease., Autophagy, 8, 997, 10.4161/auto.20748

Matus, 2011, Protein folding stress in neurodegenerative diseases: a glimpse into the ER., Curr. Opin. Cell Biol., 23, 239, 10.1016/j.ceb.2011.01.003

Matus, 2013, Functional role of the transcription factor ATF4 in the pathogenesis of amyotrophic lateral sclerosis., PLoS ONE, 8, 10.1371/journal.pone.0066672

Matus, 2009, XBP-1 deficiency in the nervous system reveals a homeostatic switch to activate autophagy., Autophagy, 5, 1226, 10.4161/auto.5.8.10247

Mazzulli, 2011, Gaucher disease glucocerebrosidase and alpha-synuclein form a bidirectional pathogenic loop in synucleinopathies., Cell, 146, 37, 10.1016/j.cell.2011.06.001

McInnes, 2013, Insights on altered mitochondrial function and dynamics in the pathogenesis of neurodegeneration., Transl. Neurodegener., 2, 10.1186/2047-9158-2-12

Mekahli, 2011, Endoplasmic-reticulum calcium depletion and disease., Cold Spring Harb. Perspect. Biol., 3, 10.1101/cshperspect.a004317

Menzies, 2015, Compromised autophagy and neurodegenerative diseases., Nat. Rev. Neurosci., 16, 345, 10.1038/nrn3961

Meusser, 2005, ERAD: the long road to destruction., Nat. Cell Biol., 7, 766, 10.1038/ncb0805-766

Mitsuda, 2007, ATF4 regulates γ-secretase activity during amino acid imbalance., Biochem. Biophys. Res. Commun., 352, 722, 10.1016/j.bbrc.2006.11.075

Mollereau, 2013, Establishing links between ER-hormesis and cancer., Mol. Cell Biol., 33, 2372, 10.1128/MCB.00315-13

Moreno, 2013, Oral treatment targeting the unfolded protein response prevents neurodegeneration and clinical disease in prion-infected mice., Sci. Transl. Med., 5, 10.1126/scitranslmed.3006767

Moreno, 2012, Sustained translational repression by eIF2α-P mediates prion neurodegeneration., Nature, 485, 507, 10.1038/nature11058

Mori, 2009, Signalling pathways in the unfolded protein response: development from yeast to mammals., J. Biochem., 146, 743, 10.1093/jb/mvp166

Moustaqim-Barrette, 2014, The amyotrophic lateral sclerosis 8 protein, VAP, is required for ER protein quality control., Hum. Mol. Genet., 23, 1975, 10.1093/hmg/ddt594

Nakagawa, 2000, Caspase-12 mediates endoplasmic-reticulum-specific apoptosis and cytotoxicity by amyloid-β., Nature, 403, 98, 10.1038/47513

Ning, 2016, β-Asarone Inhibits IRE1/XBP1 Endoplasmic Reticulum Stress Pathway in 6-OHDA-Induced Parkinsonian Rats., Neurochem. Res., 41, 2097, 10.1007/s11064-016-1922-0

Nishitoh, 2008, ALS-linked mutant SOD1 induces ER stress- and ASK1-dependent motor neuron death by targeting Derlin-1., Genes Dev., 22, 1451, 10.1101/gad.1640108

Nishitoh, 2002, ASK1 is essential for endoplasmic reticulum stress-induced neuronal cell death triggered by expanded polyglutamine repeats., Genes Dev., 16, 1345, 10.1101/gad.992302

Niwa, 1999, A role for presenilin-1 in nuclear accumulation of Ire1 fragments and induction of the mammalian unfolded protein response., Cell, 99, 691, 10.1016/S0092-8674(00)81667-0

O’Connor, 2008, Phosphorylation of the translation initiation factor eIF2α increases BACE1 levels and promotes amyloidogenesis., Neuron, 60, 988, 10.1016/j.neuron.2008.10.047

Ohoka, 2005, TRB3, a novel ER stress-inducible gene, is induced via ATF4-CHOP pathway and is involved in cell death., EMBO J., 24, 1243, 10.1038/sj.emboj.7600596

Ohta, 2011, Endoplasmic reticulum stress enhances γ-secretase activity., Biochem. Biophys. Res. Commun., 416, 362, 10.1016/j.bbrc.2011.11.042

Park, 2017, The endoplasmic reticulum chaperone GRP78/BiP modulates prion propagation in vitro and in vivo., Sci. Rep., 7, 10.1038/srep44723

Penke, 2016, Protein folding and misfolding, endoplasmic reticulum stress in neurodegenerative diseases: in trace of novel drug targets., Curr. Protein Pept. Sci., 17, 169, 10.2174/1389203716666151102104653

Prusiner, 1998, Prions., Proc. Natl. Acad. Sci. U.S.A., 95, 13363, 10.1073/pnas.95.23.13363

Puthalakath, 2007, ER stress triggers apoptosis by activating BH3-only protein Bim., Cell, 129, 1337, 10.1016/j.cell.2007.04.027

Renna, 2007, Regulation of ERGIC-53 gene transcription in response to Endoplasmic Reticulum stress., J. Biol. Chem., 282, 22499, 10.1074/jbc.M703778200

Renna, 2006, Nitric oxide-induced endoplasmic reticulum stress activates the expression of cargo receptor proteins and alters the glycoprotein transport to the Golgi complex., Int. J. Biochem. Cell Biol., 38, 2040, 10.1016/j.biocel.2006.05.016

Renna, 2011, Autophagic substrate clearance requires activity of the Syntaxin-5 SNARE complex., J. Cell Sci., 124, 469, 10.1242/jcs.076489

Ron, 2007, Signal integration in the endoplasmic reticulum unfolded protein response., Nat. Rev. Mol. Cell Biol., 8, 519, 10.1038/nrm2199

Rosenberg, 2011, Calcium signaling in neuronal development., Cold Spring Harb. Perspect. Biol., 3, 10.1101/cshperspect.a004259

Roussel, 2013, Endoplasmic reticulum dysfunction in neurological disease., Lancet Neurol., 12, 105, 10.1016/S1474-4422(12)70238-7

Rubinsztein, 2012, Autophagy modulation as a potential therapeutic target for diverse diseases., Nat. Rev. Drug Discov., 11, 709, 10.1038/nrd3802

Rutkowski, 2006, Adaptation to ER stress is mediated by differential stabilities of pro-survival and pro-apoptotic mRNAs and proteins., PLoS Biol., 4, 10.1371/journal.pbio.0040374

Safra, 2013, The ire-1 ER stress-response pathway is required for normal secretory-protein metabolism in C. elegans., J. Cell Sci., 126, 4136, 10.1242/jcs.123000

Samann, 2009, Caenorhabditits elegans LRK-1 and PINK-1 act antagonistically in stress response and neurite outgrowth., J. Biol. Chem., 284, 16482, 10.1074/jbc.M808255200

Sanchez-Martinez, 2016, Parkinson disease-linked GBA mutation effects reversed by molecular chaperones in human cell and fly models., Sci. Rep., 6, 10.1038/srep31380

Saxena, 2009, A role for motoneuron subtype-selective ER stress in disease manifestations of FALS mice., Nat. Neurosci., 12, 627, 10.1038/nn.2297

Scheper, 2015, The unfolded protein response in neurodegenerative diseases: a neuropathological perspective., Acta Neuropathol., 130, 315, 10.1007/s00401-015-1462-8

Schreiner, 2015, Amyloid-β(peptides are generated in mitochondria-associated endoplasmic reticulum membranes., J. Alzheimers Dis., 43, 369, 10.3233/JAD-132543

Schroder, 2005, The mammalian unfolded protein response., Annu. Rev. Biochem., 74, 739, 10.1146/annurev.biochem.73.011303.074134

Selkoe, 2003, Folding proteins in fatal ways., Nature, 426, 900, 10.1038/nature02264

Sellier, 2016, Loss of C9ORF72 impairs autophagy and synergizes with polyQ Ataxin-2 to induce motor neuron dysfunction and cell death., EMBO J., 35, 1276, 10.15252/embj.201593350

Selvaraj, 2012, Neurotoxin-induced ER stress in mouse dopaminergic neurons involves downregulation of TRPC1 and inhibition of AKT/mTOR signaling., J. Clin. Invest., 122, 1354, 10.1172/JCI61332

Sidrauski, 2013, Pharmacological brake-release of mRNA translation enhances cognitive memory., eLife, 2, 10.7554/eLife.00498

Sidrauski, 2015, The small molecule ISRIB reverses the effects of eIF2α phosphorylation on translation and stress granule assembly., eLife, 4, 10.7554/eLife.05033.131

Sitia, 2003, Quality control in the endoplasmic reticulum protein factory., Nature, 426, 891, 10.1038/nature02262

Soboloff, 2012, STIM proteins: dynamic calcium signal transducers., Nat. Rev. Mol. Cell Biol., 13, 549, 10.1038/nrm3414

Soto, 2012, Transmissible proteins: expanding the prion heresy., Cell, 149, 968, 10.1016/j.cell.2012.05.007

Spatuzza, 2004, Heat Shock induces preferential translation of ERGIC-53 and affects its recycling pathway., J. Biol. Chem., 279, 42535, 10.1074/jbc.M401860200

Steele, 2007, Prion pathogenesis is independent of caspase-12., Prion, 1, 243, 10.4161/pri.1.4.5551

Suzuki, 2009, ALS-linked P56S-VAPB, an aggregated loss-of-function mutant of VAPB, predisposes motor neurons to ER stress-related death by inducing aggregation of co-expressed wild-type VAPB., J. Neurochem., 108, 973, 10.1111/j.0022-3042.2008.05857.x

Tang, 2003, Huntingtin and huntingtin-associated protein 1 influence neuronal calcium signaling mediated by inositol-(1,4,5) triphosphate receptor type 1., Neuron, 39, 227, 10.1016/S0896-6273(03)00366-0

Teyssou, 2013, Mutations in SQSTM1 encoding p62 in amyotrophic lateral sclerosis: genetics and neuropathology., Acta Neuropathol., 125, 511, 10.1007/s00401-013-1090-0

Thayanidhi, 2010, α-synuclein delays endoplasmic reticulum (ER)-to-Golgi transport in mammalian cells by antagonizing ER/Golgi SNAREs., Mol. Biol. Cell, 21, 1850, 10.1091/mbc.E09-09-0801

Torres, 2010, Prion protein misfolding affects calcium homeostasis and sensitizes cells to endoplasmic reticulum stress., PLoS ONE, 5, 10.1371/journal.pone.0015658

Turner, 2005, Impaired extracellular secretion of mutant superoxide dismutase 1 associates with neurotoxicity in familial amyotrophic lateral sclerosis., J. Neurosci., 25, 108, 10.1523/JNEUROSCI.4253-04.2005

Ugolino, 2011, Mutant Atp13a2 proteins involved in parkinsonism are degraded by ER-associated degradation and sensitize cells to ER-stress induced cell death., Hum. Mol. Genet., 20, 3565, 10.1093/hmg/ddr274

Urushitani, 2006, Chromogranin-mediated secretion of mutant superoxide dismutase proteins linked to amyotrophic lateral sclerosis., Nat. Neurosci., 9, 108, 10.1038/nn1603

Uversky, 2007, Neuropathology, biochemistry, and biophysics of α-synuclein aggregation., J. Neurochem., 103, 17, 10.1111/j.1471-4159.2007.04764.x

Valastyan, 2014, Mechanisms of protein-folding diseases at a glance., Dis. Model Mech., 7, 9, 10.1242/dmm.013474

Valente, 2004, Hereditary early-onset Parkinson’s disease caused by mutations in PINK1., Science, 304, 1158, 10.1126/science.1096284

van Huizen, 2003, P58IPK, a novel endoplasmic reticulum stress-inducible protein and potential negative regulator of eIF2alpha signaling., J. Biol. Chem., 278, 15558, 10.1074/jbc.M212074200

Vidal, 2012, Targeting the UPR transcription factor XBP1 protects against Huntington’s disease through the regulation of FoxO1 and autophagy., Hum. Mol. Genet., 21, 2245, 10.1093/hmg/dds040

Vidal, 2012, Crosstalk between the UPR and autophagy pathway contributes to handling cellular stress in neurodegenerative disease., Autophagy, 8, 970, 10.4161/auto.20139

Vidal, 2014, Targeting autophagy in neurodegenerative diseases., Trends Pharmacol. Sci., 35, 583, 10.1016/j.tips.2014.09.002

Vieira, 2015, Guanabenz treatment accelerates disease in a mutant SOD1 mouse model of ALS., PLoS ONE, 10, 10.1371/journal.pone.0135570

Volgyi, 2015, Dysfunction of Endoplasmic Reticulum (ER) and Mitochondria (MT) in Alzheimer’s Disease: the role of the ER-MT cross-talk., Curr. Alzheimer Res., 12, 655, 10.2174/1567205012666150710095035

Vollrath, 2014, Loss of function of the ALS protein SigR1 leads to ER pathology associated with defective autophagy and lipid raft disturbances., Cell Death Dis., 5, 10.1038/cddis.2014.243

Walker, 2010, Protein disulphide isomerase protects against protein aggregation and is S-nitrosylated in amyotrophic lateral sclerosis., Brain, 133, 105, 10.1093/brain/awp267

Walker, 2013, ALS-associated TDP-43 induces endoplasmic reticulum stress, which drives cytoplasmic TDP-43 accumulation and stress granule formation., PLoS ONE, 8, 10.1371/journal.pone.0081170

Walter, 2011, The unfolded protein response: from stress pathway to homeostatic regulation., Science, 334, 1081, 10.1126/science.1209038

Wang, 2011, The unfolded protein response in familial amyotrophic lateral sclerosis., Hum. Mol. Genet., 20, 1008, 10.1093/hmg/ddq546

Wang, 2014, The impact of the endoplasmic reticulum protein-folding environment on cancer development., Nat. Rev. Cancer, 14, 581, 10.1038/nrc3800

Watabe, 2004, Rotenone induces apoptosis via activation of bad in human dopaminergic SH-SY5Y cells., J. Pharmacol. Exp. Ther., 311, 948, 10.1124/jpet.104.071381

Wong, 2010, Autophagy gone awry in neurodegenerative diseases., Nat. Neurosci., 13, 805, 10.1038/nn.2575

Xu, 2012, Endoplasmic reticulum stress and prion diseases., Rev. Neurosci., 23, 79, 10.1515/rns.2011.062

Yang, 2010, Huntingtin interacts with the cue domain of gp78 and inhibits gp78 binding to ubiquitin and p97/VCP., PLoS ONE, 5, 10.1371/journal.pone.0008905

Yang, 2016, Rescue of glaucomatous neurodegeneration by differentially modulating neuronal endoplasmic reticulum stress molecules., J. Neurosci., 36, 5891, 10.1523/JNEUROSCI.3709-15.2016

Yang, 2016, Repression of the eIF2α kinase PERK alleviates mGluR-LTD impairments in a mouse model of Alzheimer’s disease., Neurobiol. Aging, 41, 19, 10.1016/j.neurobiolaging.2016.02.005

Yang, 1998, The chaperone BiP/GRP78 binds to amyloid precursor protein and decreases Aβ40 and Aβ42 secretion., J. Biol. Chem., 273, 25552, 10.1074/jbc.273.40.25552

Yoon, 2012, JNK3 perpetuates metabolic stress induced by Aβ peptides., Neuron, 75, 824, 10.1016/j.neuron.2012.06.024

Yuan, 2011, Dysregulated LRRK2 signaling in response to endoplasmic reticulum stress leads to dopaminergic neuron degeneration in C. elegans., PLoS ONE, 6, 10.1371/journal.pone.0022354

Zhang, 2016, Stromal Interaction Molecule 1 rescues store-operated calcium entry and protects NG115-401L cells against cell death induced by endoplasmic reticulum and mitochondrial oxidative stress., Neurochem. Int., 97, 137, 10.1016/j.neuint.2016.04.002

Zhang, 2006, Protein folding in the endoplasmic reticulum and the unfolded protein response., Handb. Exp. Pharmacol., 172, 69, 10.1007/3-540-29717-0_3

Zhao, 2006, Endoplasmic reticulum stress in health and disease., Curr. Opin. Cell Biol., 18, 444, 10.1016/j.ceb.2006.06.005

Zhao, 2013, XBP-1u suppresses autophagy by promoting the degradation of FoxO1 in cancer cells., Cell Res., 23, 491, 10.1038/cr.2013.2

Zhou, 2011, Regulation of glucose omeostasis through a XBP-1-FoxO1 interaction., Nat. Med., 17, 356, 10.1038/nm.2293

Zhu, 2015, Allicin improves endoplasmic reticulum stress-related cognitive deficits via PERK/Nrf2 antioxidative signaling pathway., Eur. J. Pharmacol., 762, 239, 10.1016/j.ejphar.2015.06.002

Zinszner, 1998, CHOP is implicated in programmed cell death in response to impaired function of the endoplasmic reticulum., Genes Dev., 12, 982, 10.1101/gad.12.7.982