{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T00:05:32Z","timestamp":1791245132657,"version":"4.1.0"},"reference-count":210,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2021,2,26]],"date-time":"2021-02-26T00:00:00Z","timestamp":1614297600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003977","name":"Israel Science Foundation","doi-asserted-by":"publisher","award":["Legacy Heritage Fund (2394\/17)"],"award-info":[{"award-number":["Legacy Heritage Fund (2394\/17)"]}],"id":[{"id":"10.13039\/501100003977","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>With the extension of life span in recent decades, there is an increasing burden of late-onset neurodegenerative diseases, for which effective treatments are lacking. Neurodegenerative diseases include the widespread Alzheimer\u2019s disease (AD) and Parkinson\u2019s disease (PD), the less frequent Huntington\u2019s disease (HD) and Amyotrophic Lateral Sclerosis (ALS) and also rare early-onset diseases linked to mutations that cause protein aggregation or loss of function in genes that maintain protein homeostasis. The difficulties in applying gene therapy approaches to tackle these diseases is drawing increasing attention to strategies that aim to inhibit cellular toxicity and restore homeostasis by intervening in cellular pathways. These include the unfolded protein response (UPR), activated in response to endoplasmic reticulum (ER) stress, a cellular affliction that is shared by these diseases. Special focus is turned to the PKR-like ER kinase (PERK) pathway of the UPR as a target for intervention. However, the complexity of the pathway and its ability to promote cell survival or death, depending on ER stress resolution, has led to some confusion in conflicting studies. Both inhibition and activation of the PERK pathway have been reported to be beneficial in disease models, although there are also some reports where they are counterproductive. Although with the current knowledge a definitive answer cannot be given on whether it is better to activate or to inhibit the pathway, the most encouraging strategies appear to rely on boosting some steps without compromising downstream recovery.<\/jats:p>","DOI":"10.3390\/biom11030354","type":"journal-article","created":{"date-parts":[[2021,2,26]],"date-time":"2021-02-26T06:47:20Z","timestamp":1614322040000},"page":"354","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":70,"title":["PERK Pathway and Neurodegenerative Disease: To Inhibit or to Activate?"],"prefix":"10.3390","volume":"11","author":[{"given":"Talya","family":"Shacham","sequence":"first","affiliation":[{"name":"Cell Biology Division, George Wise Faculty of Life Sciences, The Shmunis School of Biomedicine and Cancer Research, Tel Aviv University, Tel Aviv 69978, Israel"},{"name":"Sagol School of Neuroscience, Tel Aviv University, Tel Aviv 69978, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6841-8225","authenticated-orcid":false,"given":"Chaitanya","family":"Patel","sequence":"additional","affiliation":[{"name":"Cell Biology Division, George Wise Faculty of Life Sciences, The Shmunis School of Biomedicine and Cancer Research, Tel Aviv University, Tel Aviv 69978, Israel"},{"name":"Sagol School of Neuroscience, Tel Aviv University, Tel Aviv 69978, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9857-7152","authenticated-orcid":false,"given":"Gerardo Z.","family":"Lederkremer","sequence":"additional","affiliation":[{"name":"Cell Biology Division, George Wise Faculty of Life Sciences, The Shmunis School of Biomedicine and Cancer Research, Tel Aviv University, Tel Aviv 69978, Israel"},{"name":"Sagol School of Neuroscience, Tel Aviv University, Tel Aviv 69978, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,2,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1038\/nrn3689","article-title":"Disturbance of endoplasmic reticulum proteostasis in neurodegenerative diseases","volume":"15","author":"Hetz","year":"2014","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1146\/annurev-cellbio-040320-120625","article-title":"Developing Therapies for Neurodegenerative Disorders: Insights from Protein Aggregation and Cellular Stress Responses","volume":"36","author":"Mallucci","year":"2020","journal-title":"Annu. Rev. Cell Dev. Biol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"658","DOI":"10.1016\/j.brainres.2016.03.044","article-title":"Protein aggregation and ER stress","volume":"1648","author":"Lederkremer","year":"2016","journal-title":"Brain Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1186\/s40035-017-0101-9","article-title":"RNAi mechanisms in Huntington\u2019s disease therapy: siRNA versus shRNA","volume":"6","author":"Aguiar","year":"2017","journal-title":"Transl. Neurodegener."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Southwell, A.L., Kordasiewicz, H.B., Langbehn, D., Skotte, N.H., Parsons, M.P., Villanueva, E.B., Caron, N.S., Ostergaard, M.E., Anderson, L.M., and Xie, Y. (2018). Huntingtin suppression restores cognitive function in a mouse model of Huntington\u2019s disease. Sci. Transl. Med., 10.","DOI":"10.1126\/scitranslmed.aar3959"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2719","DOI":"10.1172\/JCI92087","article-title":"CRISPR\/Cas9-mediated gene editing ameliorates neurotoxicity in mouse model of Huntington\u2019s disease","volume":"127","author":"Yang","year":"2017","journal-title":"J. Clin. Investig."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1177\/0960327107083417","article-title":"Hormesis and disease resistance: Activation of cellular stress response pathways","volume":"27","author":"Mattson","year":"2008","journal-title":"Hum. Exp. Toxicol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1038\/nrm829","article-title":"The unfolded protein response in nutrient sensing and differentiation","volume":"3","author":"Kaufman","year":"2002","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1038\/s41580-018-0068-0","article-title":"Linking cellular stress responses to systemic homeostasis","volume":"19","author":"Galluzzi","year":"2018","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1146\/annurev.physiol.67.040403.103635","article-title":"Molecular and evolutionary basis of the cellular stress response","volume":"67","year":"2005","journal-title":"Annu. Rev. Physiol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"a036434","DOI":"10.1101\/cshperspect.a036434","article-title":"Cell Death and Neurodegeneration","volume":"12","author":"Andreone","year":"2020","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"eabb9614","DOI":"10.1126\/sciadv.abb9614","article-title":"Beyond the cell factory: Homeostatic regulation of and by the UPR(ER)","volume":"6","author":"Metcalf","year":"2020","journal-title":"Sci. Adv."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1038\/16729","article-title":"Protein translation and folding are coupled by an endoplasmic-reticulum-resident kinase","volume":"397","author":"Harding","year":"1999","journal-title":"Nature"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1197","DOI":"10.1016\/0092-8674(93)90648-A","article-title":"Transcriptional induction of genes encoding endoplasmic reticulum resident proteins requires a transmembrane protein kinase","volume":"73","author":"Cox","year":"1993","journal-title":"Cell"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"27013","DOI":"10.1016\/S0021-9258(19)61473-0","article-title":"Activation of ATF6 and an ATF6 DNA binding site by the endoplasmic reticulum stress response","volume":"275","author":"Wang","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1016\/j.tibs.2014.08.004","article-title":"Dimerization-induced allostery in protein kinase regulation","volume":"39","author":"Lavoie","year":"2014","journal-title":"Trends Biochem. Sci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e1822","DOI":"10.1038\/cddis.2015.183","article-title":"Protein kinase R-like ER kinase and its role in endoplasmic reticulum stress-decided cell fate","volume":"6","author":"Liu","year":"2015","journal-title":"Cell Death Dis."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"11962","DOI":"10.1093\/nar\/gkx845","article-title":"Novel mechanisms of eIF2B action and regulation by eIF2\u03b1 phosphorylation","volume":"45","author":"Bogorad","year":"2017","journal-title":"Nucleic Acids Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"11269","DOI":"10.1073\/pnas.0400541101","article-title":"Reinitiation involving upstream ORFs regulates ATF4 mRNA translation in mammalian cells","volume":"101","author":"Vattem","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1011","DOI":"10.1083\/jcb.153.5.1011","article-title":"Feedback inhibition of the unfolded protein response by GADD34-mediated dephosphorylation of eIF2\u03b1","volume":"153","author":"Novoa","year":"2001","journal-title":"J. Cell Biol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1083\/jcb.200308075","article-title":"Inhibition of a constitutive translation initiation factor 2alpha phosphatase, CReP, promotes survival of stressed cells","volume":"163","author":"Jousse","year":"2003","journal-title":"J. Cell Biol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1006\/excr.2001.5248","article-title":"Stress-inducible transcription factor CHOP\/gadd153 induces apoptosis in mammalian cells via p38 kinase-dependent and -independent mechanisms","volume":"267","author":"Maytin","year":"2001","journal-title":"Exp. Cell Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"eabb6896","DOI":"10.1126\/science.abb6896","article-title":"QRICH1 dictates the outcome of ER stress through transcriptional control of proteostasis","volume":"371","author":"You","year":"2021","journal-title":"Science"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1093\/jnen\/nlz129","article-title":"The Integrated Stress Response and Phosphorylated Eukaryotic Initiation Factor 2\u03b1 in Neurodegeneration","volume":"79","author":"Bond","year":"2020","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Costa-Mattioli, M., and Walter, P. (2020). The integrated stress response: From mechanism to disease. Science, 368.","DOI":"10.1126\/science.aat5314"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1021\/tx700302s","article-title":"Covalent Modification at Cys151 Dissociates the Electrophile Sensor Keap1 from the Ubiquitin Ligase CUL3","volume":"21","author":"Rachakonda","year":"2008","journal-title":"Chem. Res. Toxicol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"16817","DOI":"10.1074\/jbc.R117.800169","article-title":"Stress-sensing mechanisms and the physiological roles of the Keap1\u2013Nrf2 system during cellular stress","volume":"292","author":"Suzuki","year":"2017","journal-title":"J. Biol. Chem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1016\/j.bbadis.2016.11.005","article-title":"Nrf2 signaling pathway: Pivotal roles in inflammation","volume":"Volume 1863","author":"Ahmed","year":"2017","journal-title":"Biochimica et Biophysica Acta Molecular Basis of Disease"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2864","DOI":"10.1073\/pnas.1212484110","article-title":"Negative feedback by IRE1\u03b2 optimizes mucin production in goblet cells","volume":"110","author":"Tsuru","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1052","DOI":"10.1038\/s41589-020-0584-z","article-title":"Pharmacologic IRE1\/XBP1s activation confers targeted ER proteostasis reprogramming","volume":"16","author":"Grandjean","year":"2020","journal-title":"Nat. Chem. Biol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"5355","DOI":"10.1016\/j.febslet.2007.10.033","article-title":"A different pathway in the endoplasmic reticulum stress-induced expression of human HRD1 and SEL1 genes","volume":"581","author":"Kaneko","year":"2007","journal-title":"FEBS Lett."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"7448","DOI":"10.1128\/MCB.23.21.7448-7459.2003","article-title":"XBP-1 Regulates a Subset of Endoplasmic Reticulum Resident Chaperone Genes in the Unfolded Protein Response","volume":"23","author":"Lee","year":"2003","journal-title":"Mol. Cell. Biol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1016\/S0092-8674(01)00611-0","article-title":"XBP1 mRNA Is Induced by ATF6 and Spliced by IRE1 in Response to ER Stress to Produce a Highly Active Transcription Factor","volume":"107","author":"Yoshida","year":"2001","journal-title":"Cell"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"118740","DOI":"10.1016\/j.lfs.2020.118740","article-title":"The molecular mechanism and functional diversity of UPR signaling sensor IRE1","volume":"265","author":"Bashir","year":"2021","journal-title":"Life Sci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1126\/science.1129631","article-title":"Decay of endoplasmic reticulum-localized mRNAs during the unfolded protein response","volume":"313","author":"Hollien","year":"2006","journal-title":"Science"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"13792","DOI":"10.1074\/jbc.M313724200","article-title":"Herp is dually regulated by both the endoplasmic reticulum stress-specific branch of the unfolded protein response and a branch that is shared with other cellular stress pathways","volume":"279","author":"Ma","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Guo, T., Zhang, D., Zeng, Y., Huang, T.Y., Xu, H., and Zhao, Y. (2020). Molecular and cellular mechanisms underlying the pathogenesis of Alzheimer\u2019s disease. Mol. Neurodegener., 15.","DOI":"10.1186\/s13024-020-00391-7"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1168","DOI":"10.1126\/science.6474172","article-title":"Alzheimer\u2019s disease: Cell-specific pathology isolates the hippocampal formation","volume":"225","author":"Hyman","year":"1984","journal-title":"Science"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1016\/j.trci.2018.06.014","article-title":"Inflammation as a central mechanism in Alzheimer\u2019s disease","volume":"4","author":"Kinney","year":"2018","journal-title":"Alzheimer\u2019s Dement. Transl. Res. Clin. Interv."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"6288","DOI":"10.1021\/bi992933h","article-title":"Alzheimer\u2019s Disease Amyloid Propagation by a Template-Dependent Dock-Lock Mechanism\u2020","volume":"39","author":"Esler","year":"2000","journal-title":"Biochemistry"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1475","DOI":"10.1016\/S0891-5849(02)01113-9","article-title":"Is oxidative damage the fundamental pathogenic mechanism of Alzheimer\u2019s and other neurodegenerative diseases?","volume":"33","author":"Perry","year":"2002","journal-title":"Free Radic. Biol. Med."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"9498","DOI":"10.1523\/JNEUROSCI.5397-12.2013","article-title":"Tau Accumulation Activates the Unfolded Protein Response by Impairing Endoplasmic Reticulum-Associated Degradation","volume":"33","author":"Abisambra","year":"2013","journal-title":"J. Neurosci."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1007\/s00401-005-1038-0","article-title":"The unfolded protein response is activated in Alzheimer\u2019s disease","volume":"110","author":"Hoozemans","year":"2005","journal-title":"Acta Neuropathol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1038\/sj.cdd.4401778","article-title":"ER stress and neurodegenerative diseases","volume":"13","author":"Lindholm","year":"2006","journal-title":"Cell Death Differ."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1007\/s12192-018-0897-y","article-title":"Amyotrophic lateral sclerosis (ALS) and Alzheimer\u2019s disease (AD) are characterised by differential activation of ER stress pathways: Focus on UPR target genes","volume":"23","author":"Montibeller","year":"2018","journal-title":"Cell Stress Chaperones"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/j.brainresbull.2017.08.007","article-title":"PERK as a hub of multiple pathogenic pathways leading to memory deficits and neurodegeneration in Alzheimer\u2019s disease","volume":"141","author":"Ohno","year":"2018","journal-title":"Brain Res. Bull."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1186\/1742-2094-6-41","article-title":"ER stress in Alzheimer\u2019s disease: A novel neuronal trigger for inflammation and Alzheimer\u2019s pathology","volume":"6","author":"Salminen","year":"2009","journal-title":"J. Neuroinflamm."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1868","DOI":"10.1016\/j.stemcr.2017.10.015","article-title":"Cell-type Dependent Alzheimer\u2019s Disease Phenotypes: Probing the Biology of Selective Neuronal Vulnerability","volume":"9","author":"Muratore","year":"2017","journal-title":"Stem Cell Rep."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1038\/sj.cdd.4401528","article-title":"Amyloid beta induces neuronal cell death through ROS-mediated ASK1 activation","volume":"12","author":"Kadowaki","year":"2005","journal-title":"Cell Death Differ."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"2119","DOI":"10.3390\/ijms15022119","article-title":"Apoptosis Signal Regulating Kinase 1 (ASK1): Potential as a Therapeutic Target for Alzheimer\u2019s Disease","volume":"15","author":"Song","year":"2014","journal-title":"Int. J. Mol. Sci."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1299","DOI":"10.1038\/nn.3486","article-title":"Suppression of eIF2\u03b1 kinases alleviates Alzheimer\u2019s disease-related plasticity and memory deficits","volume":"16","author":"Ma","year":"2013","journal-title":"Nat. Neurosci."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"101892","DOI":"10.1016\/j.pneurobio.2020.101892","article-title":"Chronic PERK induction promotes Alzheimer-like neuropathology in Down syndrome: Insights for therapeutic intervention","volume":"196","author":"Lanzillotta","year":"2021","journal-title":"Prog. Neurobiol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"3306","DOI":"10.1523\/JNEUROSCI.5367-11.2012","article-title":"Endoplasmic reticulum stress is important for the manifestations of \u03b1-synucleinopathy in vivo","volume":"32","author":"Colla","year":"2012","journal-title":"J. Neurosci."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1016\/j.bbrc.2007.01.043","article-title":"Activation of the unfolded protein response in Parkinson\u2019s disease","volume":"354","author":"Hoozemans","year":"2007","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"10690","DOI":"10.1523\/JNEUROSCI.22-24-10690.2002","article-title":"Endoplasmic reticulum stress and the unfolded protein response in cellular models of Parkinson\u2019s disease","volume":"22","author":"Ryu","year":"2002","journal-title":"J. Neurosci."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"3301","DOI":"10.1523\/JNEUROSCI.5368-11.2012","article-title":"Accumulation of toxic alpha-synuclein oligomer within endoplasmic reticulum occurs in alpha-synucleinopathy in vivo","volume":"32","author":"Colla","year":"2012","journal-title":"J. Neurosci."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1016\/j.nbd.2015.02.005","article-title":"\u03b1-Synuclein-mediated inhibition of ATF6 processing into COPII vesicles disrupts UPR signaling in Parkinson\u2019s disease","volume":"76","author":"Credle","year":"2015","journal-title":"Neurobiol. Dis."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"e42940","DOI":"10.7554\/eLife.42940","article-title":"eIF2B activator prevents neurological defects caused by a chronic integrated stress response","volume":"8","author":"Wong","year":"2019","journal-title":"eLife"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"e32733","DOI":"10.7554\/eLife.32733","article-title":"The small molecule ISRIB rescues the stability and activity of Vanishing White Matter Disease eIF2B mutant complexes","volume":"7","author":"Wong","year":"2018","journal-title":"eLife"},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Leitman, J., Barak, B., Benyair, R., Shenkman, M., Ashery, U., Hartl, F.U., and Lederkremer, G.Z. (2014). ER stress-induced eIF2-alpha phosphorylation underlies sensitivity of striatal neurons to pathogenic huntingtin. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0090803"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"2753","DOI":"10.1038\/ncomms3753","article-title":"Soluble forms of polyQ-expanded huntingtin rather than large aggregates cause endoplasmic reticulum stress","volume":"4","author":"Leitman","year":"2013","journal-title":"Nat. Commun."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1093\/hmg\/ddr445","article-title":"IRE1 plays an essential role in ER stress-mediated aggregation of mutant huntingtin via the inhibition of autophagy flux","volume":"21","author":"Lee","year":"2012","journal-title":"Hum. Mol. Genet."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1451","DOI":"10.1101\/gad.1640108","article-title":"ALS-linked mutant SOD1 induces ER stress- and ASK1-dependent motor neuron death by targeting Derlin-1","volume":"22","author":"Nishitoh","year":"2008","journal-title":"Genes. Dev."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1016\/j.neuint.2010.12.010","article-title":"Derlin-1 overexpression ameliorates mutant SOD1-induced endoplasmic reticulum stress by reducing mutant SOD1 accumulation","volume":"58","author":"Mori","year":"2011","journal-title":"Neurochem. Int."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Westergard, T., McAvoy, K., Russell, K., Wen, X., Pang, Y., Morris, B., Pasinelli, P., Trotti, D., and Haeusler, A. (2019). Repeat-associated non-AUG translation in C9orf72-ALS\/FTD is driven by neuronal excitation and stress. EMBO Mol. Med., 11.","DOI":"10.15252\/emmm.201809423"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"816","DOI":"10.1016\/j.neuron.2018.09.044","article-title":"ALS\/FTD-Linked Mutation in FUS Suppresses Intra-axonal Protein Synthesis and Drives Disease Without Nuclear Loss-of-Function of FUS","volume":"100","author":"Tadokoro","year":"2018","journal-title":"Neuron"},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Walker, A.K., Soo, K.Y., Sundaramoorthy, V., Parakh, S., Ma, Y., Farg, M.A., Wallace, R.H., Crouch, P.J., Turner, B.J., and Horne, M.K. (2013). ALS-Associated TDP-43 Induces Endoplasmic Reticulum Stress, Which Drives Cytoplasmic TDP-43 Accumulation and Stress Granule Formation. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0081170"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1038\/nature11058","article-title":"Sustained translational repression by eIF2alpha-P mediates prion neurodegeneration","volume":"485","author":"Moreno","year":"2012","journal-title":"Nature"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1136","DOI":"10.4103\/1673-5374.235013","article-title":"Subcellular localization of alpha-synuclein aggregates and their interaction with membranes","volume":"13","author":"Colla","year":"2018","journal-title":"Neural Regen. Res."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1126\/science.1129462","article-title":"\u03b1-Synuclein Blocks ER-Golgi Traffic and Rab1 Rescues Neuron Loss in Parkinson\u2019s Models","volume":"313","author":"Cooper","year":"2006","journal-title":"Science"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"195","DOI":"10.4103\/1673-5374.152366","article-title":"Impaired eIF2B activity in oligodendrocytes contributes to VWMD pathogenesis","volume":"10","author":"Lin","year":"2015","journal-title":"Neural Regen. Res."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"5733","DOI":"10.1073\/pnas.85.15.5733","article-title":"Differential loss of striatal projection neurons in Huntington disease","volume":"85","author":"Reiner","year":"1988","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1615","DOI":"10.1212\/01.WNL.0000065888.88988.6E","article-title":"Evidence for more widespread cerebral pathology in early HD: An MRI-based morphometric analysis","volume":"60","author":"Rosas","year":"2003","journal-title":"Neurology"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1097\/00005072-198511000-00003","article-title":"Neuropathological classification of Huntington\u2019s disease","volume":"44","author":"Vonsattel","year":"1985","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"20","DOI":"10.3389\/fmolb.2019.00020","article-title":"Protein Misfolding and ER Stress in Huntington\u2019s Disease","volume":"6","author":"Shacham","year":"2019","journal-title":"Front. Mol. Biosci."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1","DOI":"10.2174\/156652411794474419","article-title":"Converging pathways in the occurrence of endoplasmic reticulum (ER) stress in Huntington\u2019s disease","volume":"11","author":"Vidal","year":"2011","journal-title":"Curr. Mol. Med."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"18167","DOI":"10.1074\/jbc.M109.018325","article-title":"Rrs1 is involved in endoplasmic reticulum stress response in Huntington disease","volume":"284","author":"Carnemolla","year":"2009","journal-title":"J. Biol. Chem."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"3308","DOI":"10.1101\/gad.1673408","article-title":"Impaired ERAD and ER stress are early and specific events in polyglutamine toxicity","volume":"22","author":"Duennwald","year":"2008","journal-title":"Genes. Dev."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"950","DOI":"10.1016\/j.yexcr.2007.12.025","article-title":"Inhibition of endoplasmic reticulum stress counteracts neuronal cell death and protein aggregation caused by N-terminal mutant huntingtin proteins","volume":"314","author":"Reijonen","year":"2008","journal-title":"Exp. Cell. Res."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1128","DOI":"10.1016\/j.neuroscience.2009.07.048","article-title":"Inhibition of apoptosis signal-regulating kinase 1 reduces endoplasmic reticulum stress and nuclear huntingtin fragments in a mouse model of Huntington disease","volume":"163","author":"Cho","year":"2009","journal-title":"Neuroscience"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"11318","DOI":"10.1074\/jbc.M807620200","article-title":"SCAMP5 links endoplasmic reticulum stress to the accumulation of expanded polyglutamine protein aggregates via endocytosis inhibition","volume":"284","author":"Noh","year":"2009","journal-title":"J. Biol. Chem."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"2245","DOI":"10.1093\/hmg\/dds040","article-title":"Targeting the UPR transcription factor XBP1 protects against Huntington\u2019s disease through the regulation of FoxO1 and autophagy","volume":"21","author":"Vidal","year":"2012","journal-title":"Hum. Mol. Genet."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1016\/j.brainres.2016.03.034","article-title":"Endoplasmic reticulum stress: The cause and solution to Huntington\u2019s disease?","volume":"1648","author":"Jiang","year":"2016","journal-title":"Brain Res."},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"Shenkman, M., Eiger, H., and Lederkremer Gerardo, Z. (2015). Genesis of ER Stress in Huntington\u2019s Disease. Endoplasmic Reticulum Stress Dis., 2.","DOI":"10.1515\/ersc-2015-0007"},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Yang, H., Liu, C., Zhong, Y., Luo, S., Monteiro, M.J., and Fang, S. (2010). Huntingtin interacts with the cue domain of gp78 and inhibits gp78 binding to ubiquitin and p97\/VCP. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0008905"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"6410","DOI":"10.1038\/srep06410","article-title":"Aggregation of polyglutamine-expanded ataxin-3 sequesters its specific interacting partners into inclusions: Implication in a loss-of-function pathology","volume":"4","author":"Yang","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"6875","DOI":"10.1038\/s41598-020-63899-4","article-title":"A novel specific PERK activator reduces toxicity and extends survival in Huntington\u2019s disease models","volume":"10","author":"Ganz","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1062","DOI":"10.1111\/j.1471-4159.2009.06388.x","article-title":"Sequestosome 1\/p62 links familial ALS mutant SOD1 to LC3 via an ubiquitin-independent mechanism","volume":"111","author":"Gal","year":"2009","journal-title":"J. Neurochem."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"935","DOI":"10.1016\/j.cell.2016.07.001","article-title":"UBQLN2 Mediates Autophagy-Independent Protein Aggregate Clearance by the Proteasome","volume":"166","author":"Hjerpe","year":"2016","journal-title":"Cell"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1186\/s40478-019-0758-7","article-title":"Key role of UBQLN2 in pathogenesis of amyotrophic lateral sclerosis and frontotemporal dementia","volume":"7","author":"Renaud","year":"2019","journal-title":"Acta Neuropathol. Commun."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"E11485","DOI":"10.1073\/pnas.1811997115","article-title":"Ubiquilin 2 modulates ALS\/FTD-linked FUS-RNA complex dynamics and stress granule formation","volume":"115","author":"Alexander","year":"2018","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1007\/s12035-009-8054-3","article-title":"ER Stress and Unfolded Protein Response in Amyotrophic Lateral Sclerosis","volume":"39","author":"Kanekura","year":"2009","journal-title":"Mol. Neurobiol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1007\/s00401-015-1468-2","article-title":"Rab1-dependent ER\u2013Golgi transport dysfunction is a common pathogenic mechanism in SOD1, TDP-43 and FUS-associated ALS","volume":"130","author":"Soo","year":"2015","journal-title":"Acta Neuropathol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"2668","DOI":"10.1038\/s41467-018-05127-2","article-title":"A small-molecule inhibitor of SOD1-Derlin-1 interaction ameliorates pathology in an ALS mouse model","volume":"9","author":"Tsuburaya","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"1008","DOI":"10.1093\/hmg\/ddq546","article-title":"The unfolded protein response in familial amyotrophic lateral sclerosis","volume":"20","author":"Wang","year":"2011","journal-title":"Hum. Mol. Genet."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1016\/j.nbd.2019.03.024","article-title":"The UPR-PERK pathway is not a promising therapeutic target for mutant SOD1-induced ALS","volume":"127","author":"Dzhashiashvili","year":"2019","journal-title":"Neurobiol. Dis."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1007\/s00401-010-0700-3","article-title":"Cellular and sub-cellular pathology of animal prion diseases: Relationship between morphological changes, accumulation of abnormal prion protein and clinical disease","volume":"121","author":"Jeffrey","year":"2011","journal-title":"Acta Neuropathol."},{"key":"ref_98","doi-asserted-by":"crossref","unstructured":"Chiesa, R. (2015). The elusive role of the prion protein and the mechanism of toxicity in prion disease. PLoS Pathog., 11.","DOI":"10.1371\/journal.ppat.1004745"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1016\/j.brainres.2016.04.009","article-title":"The stress of prion disease","volume":"1648","author":"Mays","year":"2016","journal-title":"Brain Res."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"684","DOI":"10.1016\/j.tips.2019.07.003","article-title":"Small Molecules to Improve ER Proteostasis in Disease","volume":"40","author":"Auyeung","year":"2019","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"812","DOI":"10.1111\/jnc.14112","article-title":"Fine-tuning PERK signaling for neuroprotection","volume":"142","author":"Halliday","year":"2017","journal-title":"J. Neurochem."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1111\/febs.14422","article-title":"The unfolded protein response in neurodegenerative disorders\u2014Therapeutic modulation of the PERK pathway","volume":"286","author":"Hughes","year":"2019","journal-title":"FEBS J."},{"key":"ref_103","doi-asserted-by":"crossref","unstructured":"Rozpedek-Kaminska, W., Siwecka, N., Wawrzynkiewicz, A., Wojtczak, R., Pytel, D., Diehl, J.A., and Majsterek, I. (2020). The PERK-Dependent Molecular Mechanisms as a Novel Therapeutic Target for Neurodegenerative Diseases. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21062108"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1038\/nsmb.3478","article-title":"Fine-tuning PERK signaling to control cell fate under stress","volume":"24","author":"Urra","year":"2017","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"2301","DOI":"10.2337\/diabetes.51.7.2301","article-title":"Loss of kinase activity in a patient with Wolcott-Rallison syndrome caused by a novel mutation in the EIF2AK3 gene","volume":"51","author":"Vaccaro","year":"2002","journal-title":"Diabetes"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1038\/78085","article-title":"EIF2AK3, encoding translation initiation factor 2-alpha kinase 3, is mutated in patients with Wolcott-Rallison syndrome","volume":"25","author":"Nicolino","year":"2000","journal-title":"Nat. Genet."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1186\/1750-1172-5-29","article-title":"Wolcott-Rallison syndrome","volume":"5","author":"Julier","year":"2010","journal-title":"Orphanet. J. Rare Dis."},{"key":"ref_108","first-page":"3951","article-title":"Tauopathy-associated PERK alleles are functional hypomorphs that increase neuronal vulnerability to ER stress","volume":"27","author":"Yuan","year":"2018","journal-title":"Hum. Mol. Genet."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"11350","DOI":"10.1523\/JNEUROSCI.1637-16.2016","article-title":"Ablation of Perk in Schwann Cells Improves Myelination in the S63del Charcot-Marie-Tooth 1B Mouse","volume":"36","author":"Sidoli","year":"2016","journal-title":"J. Neurosci."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"2629","DOI":"10.1093\/hmg\/ddt658","article-title":"An enhanced integrated stress response ameliorates mutant SOD1-induced ALS","volume":"23","author":"Wang","year":"2014","journal-title":"Hum. Mol. Genet."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"935","DOI":"10.1126\/science.1101902","article-title":"A selective inhibitor of eIF2alpha dephosphorylation protects cells from ER stress","volume":"307","author":"Boyce","year":"2005","journal-title":"Science"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"901","DOI":"10.1523\/JNEUROSCI.4289-06.2007","article-title":"Endoplasmic reticulum stress inhibition protects against excitotoxic neuronal injury in the rat brain","volume":"27","author":"Sokka","year":"2007","journal-title":"J. Neurosci."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.nlm.2019.03.002","article-title":"Salubrinal offers neuroprotection through suppressing endoplasmic reticulum stress, autophagy and apoptosis in a mouse traumatic brain injury model","volume":"161","author":"Wang","year":"2019","journal-title":"Neurobiol. Learn. Memory"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.brainres.2014.01.003","article-title":"Salubrinal protects against rotenone-induced SH-SY5Y cell death via ATF4-parkin pathway","volume":"1549","author":"Wu","year":"2014","journal-title":"Brain Res."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1126\/science.1201396","article-title":"Selective inhibition of a regulatory subunit of protein phosphatase 1 restores proteostasis","volume":"332","author":"Tsaytler","year":"2011","journal-title":"Science"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1016\/j.nbd.2014.08.010","article-title":"Guanabenz, which enhances the unfolded protein response, ameliorates mutant SOD1-induced amyotrophic lateral sclerosis","volume":"71","author":"Wang","year":"2014","journal-title":"Neurobiol. Dis."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1111\/nan.12411","article-title":"Bergmann glia translocation: A new disease marker for vanishing white matter identifies therapeutic effects of Guanabenz treatment","volume":"44","author":"Dooves","year":"2018","journal-title":"Neuropathol. Appl. Neurobiol."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.1016\/S0896-6273(02)01125-X","article-title":"Parkin protects against the toxicity associated with mutant \u03b1-Synuclein: Proteasome dysfunction selectively affects catecholaminergic neurons","volume":"36","author":"Petrucelli","year":"2002","journal-title":"Neuron"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.expneurol.2018.01.015","article-title":"Guanabenz promotes neuronal survival via enhancement of ATF4 and parkin expression in models of Parkinson disease","volume":"303","author":"Sun","year":"2018","journal-title":"Exp. Neurol."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"1357","DOI":"10.1523\/JNEUROSCI.3365-12.2013","article-title":"Declines in Drp1 and parkin expression underlie DNA damage-induced changes in mitochondrial length and neuronal death","volume":"33","author":"Wang","year":"2013","journal-title":"J. Neurosci."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"834","DOI":"10.3389\/fonc.2020.00834","article-title":"Salubrinal in Combination With 4E1RCat Synergistically Impairs Melanoma Development by Disrupting the Protein Synthetic Machinery","volume":"10","author":"Kardos","year":"2020","journal-title":"Front. Oncol."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"13671","DOI":"10.1038\/s41598-020-70689-5","article-title":"Administration of small-molecule guanabenz acetate attenuates fatty liver and hyperglycemia associated with obesity","volume":"10","author":"Yoshino","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1126\/science.aaa4484","article-title":"Preventing proteostasis diseases by selective inhibition of a phosphatase regulatory subunit","volume":"348","author":"Das","year":"2015","journal-title":"Science"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1093\/brain\/awy322","article-title":"Sephin1, which prolongs the integrated stress response, is a promising therapeutic for multiple sclerosis","volume":"142","author":"Chen","year":"2019","journal-title":"Brain"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"2206","DOI":"10.1007\/s12035-020-01880-y","article-title":"Sephin1 Reduces Prion Infection in Prion-Infected Cells and Animal Model","volume":"57","author":"Thapa","year":"2020","journal-title":"Mol. Neurobiol."},{"key":"ref_126","doi-asserted-by":"crossref","unstructured":"Crespillo-Casado, A., Chambers, J.E., Fischer, P.M., Marciniak, S.J., and Ron, D. (2017). PPP1R15A-mediated dephosphorylation of eIF2\u03b1 is unaffected by Sephin1 or Guanabenz. eLife, 6.","DOI":"10.7554\/eLife.26109"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"3575","DOI":"10.1021\/acschemneuro.9b00185","article-title":"PromISR-6, a Guanabenz Analogue, Improves Cellular Survival in an Experimental Model of Huntington\u2019s Disease","volume":"10","author":"Sundaram","year":"2019","journal-title":"ACS Chem. Neurosci."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"1216","DOI":"10.1016\/j.cell.2018.06.030","article-title":"Target-Based Discovery of an Inhibitor of the Regulatory Phosphatase PPP1R15B","volume":"174","author":"Krzyzosiak","year":"2018","journal-title":"Cell"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"371","DOI":"10.15252\/emmm.201606664","article-title":"PERK activation mitigates tau pathology in vitro and in vivo","volume":"9","author":"Bruch","year":"2017","journal-title":"EMBO Mol. Med."},{"key":"ref_130","doi-asserted-by":"crossref","unstructured":"Mori, T., Hayashi, T., Hayashi, E., and Su, T.P. (2013). Sigma-1 receptor chaperone at the ER-mitochondrion interface mediates the mitochondrion-ER-nucleus signaling for cellular survival. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0076941"},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1016\/j.nbd.2018.01.004","article-title":"Targeting PERK signaling with the small molecule GSK2606414 prevents neurodegeneration in a model of Parkinson\u2019s disease","volume":"112","author":"Mercado","year":"2018","journal-title":"Neurobiol. Dis."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1007\/s00401-015-1487-z","article-title":"PERK inhibition prevents tau-mediated neurodegeneration in a mouse model of frontotemporal dementia","volume":"130","author":"Radford","year":"2015","journal-title":"Acta Neuropathol."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.neurobiolaging.2016.02.005","article-title":"Repression of the eIF2\u03b1 kinase PERK alleviates mGluR-LTD impairments in a mouse model of Alzheimer\u2019s disease","volume":"41","author":"Yang","year":"2016","journal-title":"Neurobiol. Aging"},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"1100","DOI":"10.1038\/cdd.2017.58","article-title":"When PERK inhibitors turn out to be new potent RIPK1 inhibitors: Critical issues on the specificity and use of GSK2606414 and GSK2656157","volume":"24","author":"Delvaeye","year":"2017","journal-title":"Cell Death Differ."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"5900","DOI":"10.1523\/JNEUROSCI.2343-16.2017","article-title":"Activation of PERK Elicits Memory Impairment through Inactivation of CREB and Downregulation of PSD95 After Traumatic Brain Injury","volume":"37","author":"Sen","year":"2017","journal-title":"J. Neurosci."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1007\/s10522-017-9738-0","article-title":"Echinacoside, a phenylethanoid glycoside from Cistanche deserticola, extends lifespan of Caenorhabditis elegans and protects from Abeta-induced toxicity","volume":"19","author":"Chen","year":"2018","journal-title":"Biogerontology"},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"1403","DOI":"10.3389\/fcell.2020.593659","article-title":"Echinacoside Suppresses Amyloidogenesis and Modulates F-actin Remodeling by Targeting the ER Stress Sensor PERK in a Mouse Model of Alzheimer\u2019s Disease","volume":"8","author":"Dai","year":"2020","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1016\/j.brainres.2010.05.018","article-title":"Neurotrophic and neurorescue effects of Echinacoside in the subacute MPTP mouse model of Parkinson\u2019s disease","volume":"1346","author":"Zhao","year":"2010","journal-title":"Brain Res."},{"key":"ref_139","doi-asserted-by":"crossref","unstructured":"Wu, C.J., Chien, M.Y., Lin, N.H., Lin, Y.C., Chen, W.Y., Chen, C.H., and Tzen, J.T.C. (2019). Echinacoside Isolated from Cistanche tubulosa Putatively Stimulates Growth Hormone Secretion via Activation of the Ghrelin Receptor. Molecules, 24.","DOI":"10.3390\/molecules24040720"},{"key":"ref_140","first-page":"1195","article-title":"Echinacoside-induced nitric oxide production in endothelial cells: Roles of androgen receptor and the PI3K-Akt pathway","volume":"45","author":"Gu","year":"2020","journal-title":"Int. J. Mol. Med."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"eabb4749","DOI":"10.1126\/scisignal.abb4749","article-title":"Targeting the kinase insert loop of PERK selectively modulates PERK signaling without systemic toxicity in mice","volume":"13","author":"Hughes","year":"2020","journal-title":"Sci. Signal."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1038\/s41419-020-2601-2","article-title":"Fine tuning of the unfolded protein response by ISRIB improves neuronal survival in a model of amyotrophic lateral sclerosis","volume":"Volume 11","author":"Bugallo","year":"2020","journal-title":"Cell Death Disease"},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1016\/j.jphs.2016.08.003","article-title":"Unique pharmacological property of ISRIB in inhibition of A\u03b2-induced neuronal cell death","volume":"131","author":"Hosoi","year":"2016","journal-title":"J. Pharmacol. Sci."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"E6420","DOI":"10.1073\/pnas.1707661114","article-title":"Inhibition of the integrated stress response reverses cognitive deficits after traumatic brain injury","volume":"114","author":"Chou","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"1768","DOI":"10.1093\/brain\/awx074","article-title":"Repurposed drugs targeting eIF2\u03b1-P-mediated translational repression prevent neurodegeneration in mice","volume":"140","author":"Halliday","year":"2017","journal-title":"Brain"},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"1355","DOI":"10.1007\/s00702-017-1830-8","article-title":"Trazodone alleviates both dyskinesia and psychosis in the parkinsonian marmoset model of Parkinson\u2019s disease","volume":"125","author":"Hamadjida","year":"2018","journal-title":"J. Neural Transm."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"473","DOI":"10.2174\/157340608785700199","article-title":"Dibenzoylmethane activates Nrf2-dependent detoxification pathway and inhibits benzo(a)pyrene induced DNA adducts in lungs","volume":"4","author":"Thimmulappa","year":"2008","journal-title":"Med. Chem."},{"key":"ref_148","doi-asserted-by":"crossref","unstructured":"Kim, N., Kim, H.M., Lee, E.S., Lee, J.O., Lee, H.J., Lee, S.K., Moon, J.W., Kim, J.H., Kim, J.K., and Kim, S.J. (2015). Dibenzoylmethane exerts metabolic activity through regulation of AMP-activated protein kinase (AMPK)-mediated glucose uptake and adipogenesis pathways. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0120104"},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1016\/j.neuropharm.2007.05.011","article-title":"Trazodone inhibits T-type calcium channels","volume":"53","author":"Kraus","year":"2007","journal-title":"Neuropharmacology"},{"key":"ref_150","doi-asserted-by":"crossref","unstructured":"Aton, S.J., Seibt, J., Dumoulin, M.C., Coleman, T., Shiraishi, M., and Frank, M.G. (2009). The Sedating Antidepressant Trazodone Impairs Sleep-Dependent Cortical Plasticity. PLoS ONE, 4.","DOI":"10.1371\/journal.pone.0006078"},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"113834","DOI":"10.1016\/j.bcp.2020.113834","article-title":"In silico screening of GMQ-like compounds reveals guanabenz and sephin1 as new allosteric modulators of acid-sensing ion channel 3","volume":"174","author":"Callejo","year":"2020","journal-title":"Biochem. Pharmacol."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"828","DOI":"10.1016\/j.cellsig.2015.01.010","article-title":"Salubrinal acts as a Dusp2 inhibitor and suppresses inflammation in anti-collagen antibody-induced arthritis","volume":"27","author":"Hamamura","year":"2015","journal-title":"Cell. Signal."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"1013","DOI":"10.1016\/j.bbrc.2020.03.097","article-title":"Bruceine D elevates Nrf2 activation to restrain Parkinson\u2019s disease in mice through suppressing oxidative stress and inflammatory response","volume":"526","author":"Yang","year":"2020","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/j.canlet.2017.06.014","article-title":"Bruceine D inhibits hepatocellular carcinoma growth by targeting \u03b2-catenin\/jagged1 pathways","volume":"403","author":"Cheng","year":"2017","journal-title":"Cancer Lett."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"109089","DOI":"10.1016\/j.biopha.2019.109089","article-title":"Bruceine D induces apoptosis in human non-small cell lung cancer cells through regulating JNK pathway","volume":"117","author":"Tan","year":"2019","journal-title":"Biomed. Pharmacother."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1016\/j.phrs.2018.11.043","article-title":"Naringenin targets on astroglial Nrf2 to support dopaminergic neurons","volume":"139","author":"Wang","year":"2019","journal-title":"Pharmacol. Res."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/j.ejphar.2015.07.001","article-title":"Naringenin improves learning and memory in an Alzheimer\u2019s disease rat model: Insights into the underlying mechanisms","volume":"764","author":"Ghofrani","year":"2015","journal-title":"Eur. J. Pharmacol."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1016\/j.compbiomed.2018.05.012","article-title":"Across the blood-brain barrier: Neurotherapeutic screening and characterization of naringenin as a novel CRMP-2 inhibitor in the treatment of Alzheimer\u2019s disease using bioinformatics and computational tools","volume":"98","author":"Lawal","year":"2018","journal-title":"Comput. Biol. Med."},{"key":"ref_159","first-page":"215","article-title":"Inhibition of 6-hydroxydopamine-induced endoplasmic reticulum stress by sulforaphane through the activation of Nrf2 nuclear translocation","volume":"6","author":"Deng","year":"2012","journal-title":"Mol. Med. Rep."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"2347","DOI":"10.1089\/ars.2010.3731","article-title":"Pharmacological targeting of the transcription factor Nrf2 at the basal ganglia provides disease modifying therapy for experimental parkinsonism","volume":"14","author":"Jazwa","year":"2011","journal-title":"Antioxid. Redox Signal."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.neuro.2013.03.004","article-title":"Neuroprotective effect of sulforaphane in 6-hydroxydopamine-lesioned mouse model of Parkinson\u2019s disease","volume":"36","author":"Morroni","year":"2013","journal-title":"Neurotoxicology"},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1111\/jnc.12647","article-title":"Sulforaphane enhances proteasomal and autophagic activities in mice and is a potential therapeutic reagent for Huntington\u2019s disease","volume":"129","author":"Liu","year":"2014","journal-title":"J. Neurochem."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"1803","DOI":"10.3233\/JAD-171110","article-title":"Sulforaphane Inhibits the Generation of Amyloid-\u03b2 Oligomer and Promotes Spatial Learning and Memory in Alzheimer\u2019s Disease (PS1V97L) Transgenic Mice","volume":"62","author":"Hou","year":"2018","journal-title":"J. Alzheimers Dis."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"7","DOI":"10.3109\/13506129.2012.751367","article-title":"Amelioration of Alzheimer\u2019s disease by neuroprotective effect of sulforaphane in animal model","volume":"20","author":"Kim","year":"2013","journal-title":"Amyloid"},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"127","DOI":"10.3233\/JAD-200397","article-title":"Sulforaphane Reverses the Amyloid-\u03b2 Oligomers Induced Depressive-Like Behavior","volume":"78","author":"Wang","year":"2020","journal-title":"J. Alzheimers Dis."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1177\/1533317514542645","article-title":"Sulforaphane ameliorates neurobehavioral deficits and protects the brain from amyloid \u03b2 deposits and peroxidation in mice with Alzheimer-like lesions","volume":"30","author":"Zhang","year":"2015","journal-title":"Am. J. Alzheimers Dis. Other Demen."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1016\/j.expneurol.2013.10.002","article-title":"Sulforaphane ameliorates the development of experimental autoimmune encephalomyelitis by antagonizing oxidative stress and Th17-related inflammation in mice","volume":"250","author":"Li","year":"2013","journal-title":"Exp. Neurol."},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1016\/j.phrs.2015.05.015","article-title":"Targeting lipid peroxidation and mitochondrial imbalance in Friedreich\u2019s ataxia","volume":"99","author":"Abeti","year":"2015","journal-title":"Pharmacol. Res."},{"key":"ref_169","doi-asserted-by":"crossref","unstructured":"Youn, K., Yoon, J.H., Lee, N., Lim, G., Lee, J., Sang, S., Ho, C.T., and Jun, M. (2020). Discovery of Sulforaphane as a Potent BACE1 Inhibitor Based on Kinetics and Computational Studies. Nutrients, 12.","DOI":"10.3390\/nu12103026"},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"32008","DOI":"10.1074\/jbc.M104794200","article-title":"Nuclear factor kappa B is a molecular target for sulforaphane-mediated anti-inflammatory mechanisms","volume":"276","author":"Heiss","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/j.exger.2017.06.009","article-title":"3-NP-induced Huntington\u2019s-like disease impairs Nrf2 activation without loss of cardiac function in aged rats","volume":"96","author":"Garibay","year":"2017","journal-title":"Exp. Gerontol."},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"767","DOI":"10.3233\/JAD-2011-110512","article-title":"Therapeutic Potential and Anti-Amyloidosis Mechanisms of Tert-Butylhydroquinone for Alzheimer\u2019s Disease","volume":"26","author":"Akhter","year":"2011","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"1901","DOI":"10.1016\/j.neurobiolaging.2014.01.143","article-title":"Primary cultured astrocytes from old rats are capable to activate the Nrf2 response against MPP+ toxicity after tBHQ pretreatment","volume":"35","author":"Lazzarini","year":"2014","journal-title":"Neurobiol. Aging"},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"188","DOI":"10.3389\/fncel.2018.00188","article-title":"Novel Nrf2-Inducer Prevents Mitochondrial Defects and Oxidative Stress in Friedreich\u2019s Ataxia Models","volume":"12","author":"Abeti","year":"2018","journal-title":"Front. Cell. Neurosci."},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1093\/brain\/awq386","article-title":"Fumaric acid esters exert neuroprotective effects in neuroinflammation via activation of the Nrf2 antioxidant pathway","volume":"134","author":"Linker","year":"2011","journal-title":"Brain"},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1089\/ars.2016.6800","article-title":"The Neuroprotective Effect of Dimethyl Fumarate in an MPTP-Mouse Model of Parkinson\u2019s Disease: Involvement of Reactive Oxygen Species\/Nuclear Factor-\u03baB\/Nuclear Transcription Factor Related to NF-E2","volume":"27","author":"Campolo","year":"2017","journal-title":"Antioxid. Redox Signal."},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/j.neuroscience.2014.11.047","article-title":"Dimethyl fumarate attenuates 6-OHDA-induced neurotoxicity in SH-SY5Y cells and in animal model of Parkinson\u2019s disease by enhancing Nrf2 activity","volume":"286","author":"Jing","year":"2015","journal-title":"Neuroscience"},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"4344","DOI":"10.1038\/s41467-018-06787-w","article-title":"Dimethyl fumarate is an allosteric covalent inhibitor of the p90 ribosomal S6 kinases","volume":"9","author":"Andersen","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"1","DOI":"10.2147\/PTT.S234151","article-title":"Dimethyl Fumarate Targets MSK1, RSK1, 2 and IKK\u03b1\/\u03b2 Kinases and Regulates NF-\u03baB \/p65 Activation in Psoriasis: A Demonstration of the Effect on Peripheral Blood Mononuclear Cells, Drawn from Two Patients with Severe Psoriasis Before and After Treatment with Dimethyl Fumarate","volume":"10","author":"Gesser","year":"2020","journal-title":"Psoriasis"},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1074\/mcp.RA118.000922","article-title":"Identification of Novel Protein Targets of Dimethyl Fumarate Modification in Neurons and Astrocytes Reveals Actions Independent of Nrf2 Stabilization","volume":"18","author":"Piroli","year":"2019","journal-title":"Mol. Cell. Proteom."},{"key":"ref_181","doi-asserted-by":"crossref","unstructured":"Demmings, M.D., Tennyson, E.C., Petroff, G.N., Tarnowski-Garner, H.E., and Cregan, S.P. (2020). Activating transcription factor-4 promotes neuronal death induced by Parkinson\u2019s disease neurotoxins and \u03b1-synuclein aggregates. Cell Death Differ., in press.","DOI":"10.1038\/s41418-020-00688-6"},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.neulet.2016.05.039","article-title":"Up-regulation of activating transcription factor 4 induces severe loss of dopamine nigral neurons in a rat model of Parkinson\u2019s disease","volume":"627","author":"Gully","year":"2016","journal-title":"Neurosci. Lett."},{"key":"ref_183","doi-asserted-by":"crossref","unstructured":"Inoue, T., Yamakage, H., Tanaka, M., Kusakabe, T., Shimatsu, A., and Satoh-Asahara, N. (2019). Oxytocin Suppresses Inflammatory Responses Induced by Lipopolysaccharide through Inhibition of the eIF-2\u03b1\u2013ATF4 Pathway in Mouse Microglia. Cells, 8.","DOI":"10.3390\/cells8060527"},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"e124232","DOI":"10.1172\/jci.insight.124232","article-title":"Neuron-specific PERK inactivation exacerbates neurodegeneration during experimental autoimmune encephalomyelitis","volume":"4","author":"Stone","year":"2019","journal-title":"JCI Insight"},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"3576","DOI":"10.1111\/febs.14379","article-title":"The role of Nrf2 signaling in counteracting neurodegenerative diseases","volume":"285","author":"Kostov","year":"2018","journal-title":"FEBS J."},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1016\/j.bbrc.2015.08.016","article-title":"Pharmacokinetics and pharmacodynamics of orally administered acetylenic tricyclic bis(cyanoenone), a highly potent Nrf2 activator with a reversible covalent mode of action","volume":"465","author":"Kostov","year":"2015","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1016\/j.freeradbiomed.2015.05.028","article-title":"Sulforaphane protects the heart from doxorubicin-induced toxicity","volume":"86","author":"Singh","year":"2015","journal-title":"Free Radic. Biol. Med."},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1038\/s41419-020-2317-3","article-title":"Bruceine D induces lung cancer cell apoptosis and autophagy via the ROS\/MAPK signaling pathway in vitro and in vivo","volume":"11","author":"Fan","year":"2020","journal-title":"Cell Death Dis."},{"key":"ref_189","first-page":"819","article-title":"Bruceine D induces apoptosis in human chronic myeloid leukemia K562 cells via mitochondrial pathway","volume":"6","author":"Zhang","year":"2016","journal-title":"Am. J. Cancer Res."},{"key":"ref_190","doi-asserted-by":"crossref","unstructured":"Stockwell, S.R., Platt, G., Barrie, S.E., Zoumpoulidou, G., te Poele, R.H., Aherne, G.W., Wilson, S.C., Sheldrake, P., McDonald, E., and Venet, M. (2012). Mechanism-Based Screen for G1\/S Checkpoint Activators Identifies a Selective Activator of EIF2AK3\/PERK Signalling. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0028568"},{"key":"ref_191","doi-asserted-by":"crossref","first-page":"737","DOI":"10.3389\/fphar.2020.00737","article-title":"CCT020312 Inhibits Triple-Negative Breast Cancer Through PERK Pathway-Mediated G1 Phase Cell Cycle Arrest and Apoptosis","volume":"11","author":"Li","year":"2020","journal-title":"Front. Pharmacol."},{"key":"ref_192","doi-asserted-by":"crossref","first-page":"480","DOI":"10.1111\/j.1747-0285.2010.01048.x","article-title":"Structural determinants of PERK inhibitor potency and selectivity","volume":"76","author":"Wang","year":"2010","journal-title":"Chem. Biol. Drug Des."},{"key":"ref_193","doi-asserted-by":"crossref","first-page":"2799","DOI":"10.1093\/hmg\/9.19.2799","article-title":"Dominant phenotypes produced by the HD mutation in STHdh(Q111) striatal cells","volume":"9","author":"Trettel","year":"2000","journal-title":"Hum. Mol. Genet."},{"key":"ref_194","doi-asserted-by":"crossref","unstructured":"Vieira, F.G., Ping, Q., Moreno, A.J., Kidd, J.D., Thompson, K., Jiang, B., Lincecum, J.M., Wang, M.Z., De Zutter, G.S., and Tassinari, V.R. (2015). Guanabenz Treatment Accelerates Disease in a Mutant SOD1 Mouse Model of ALS. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0135570"},{"key":"ref_195","doi-asserted-by":"crossref","first-page":"1659","DOI":"10.1210\/en.2016-1773","article-title":"Guanabenz Sensitizes Pancreatic \u03b2 Cells to Lipotoxic Endoplasmic Reticulum Stress and Apoptosis","volume":"158","author":"Abdulkarim","year":"2017","journal-title":"Endocrinology"},{"key":"ref_196","doi-asserted-by":"crossref","first-page":"3989","DOI":"10.1074\/jbc.M607627200","article-title":"Selective inhibition of eukaryotic translation initiation factor 2 alpha dephosphorylation potentiates fatty acid-induced endoplasmic reticulum stress and causes pancreatic beta-cell dysfunction and apoptosis","volume":"282","author":"Cnop","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_197","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1016\/j.tcb.2020.09.002","article-title":"When Endoplasmic Reticulum Proteostasis Meets the DNA Damage Response","volume":"30","author":"Blondel","year":"2020","journal-title":"Trends Cell Biol."},{"key":"ref_198","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1097\/ALN.0000000000003078","article-title":"Endoplasmic Reticulum Stress Contributes to Nociception via Neuroinflammation in a Murine Bone Cancer Pain Model","volume":"132","author":"Mao","year":"2020","journal-title":"Anesthesiology"},{"key":"ref_199","doi-asserted-by":"crossref","first-page":"812","DOI":"10.1002\/biof.1380","article-title":"The combination of digoxin and GSK2606414 exerts synergistic anticancer activity against leukemia in vitro and in vivo","volume":"43","author":"Zhang","year":"2017","journal-title":"Biofactors"},{"key":"ref_200","doi-asserted-by":"crossref","first-page":"988","DOI":"10.1016\/j.neuron.2008.10.047","article-title":"Phosphorylation of the translation initiation factor eIF2alpha increases BACE1 levels and promotes amyloidogenesis","volume":"60","author":"Sadleir","year":"2008","journal-title":"Neuron"},{"key":"ref_201","doi-asserted-by":"crossref","first-page":"1993","DOI":"10.1158\/0008-5472.CAN-12-3109","article-title":"Characterization of a novel PERK kinase inhibitor with antitumor and antiangiogenic activity","volume":"73","author":"Atkins","year":"2013","journal-title":"Cancer Res."},{"key":"ref_202","first-page":"44338","article-title":"Uncoupling proteostasis and development in vitro with a small molecule inhibitor of the pancreatic endoplasmic reticulum kinase, PERK","volume":"287","author":"Harding","year":"2012","journal-title":"Trends Cell Biol."},{"key":"ref_203","doi-asserted-by":"crossref","first-page":"e00498","DOI":"10.7554\/eLife.00498","article-title":"Pharmacological brake-release of mRNA translation enhances cognitive memory","volume":"2","author":"Sidrauski","year":"2013","journal-title":"eLife"},{"key":"ref_204","doi-asserted-by":"crossref","unstructured":"Tsai, J.C., Miller-Vedam, L.E., Anand, A.A., Jaishankar, P., Nguyen, H.C., Renslo, A.R., Frost, A., and Walter, P. (2018). Structure of the nucleotide exchange factor eIF2B reveals mechanism of memory-enhancing molecule. Science, 359.","DOI":"10.1126\/science.aaq0939"},{"key":"ref_205","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/j.molcel.2020.10.031","article-title":"ISRIB Blunts the Integrated Stress Response by Allosterically Antagonising the Inhibitory Effect of Phosphorylated eIF2 on eIF2B","volume":"81","author":"Zyryanova","year":"2021","journal-title":"Mol. Cell"},{"key":"ref_206","doi-asserted-by":"crossref","first-page":"1533","DOI":"10.1126\/science.aar5129","article-title":"Binding of ISRIB reveals a regulatory site in the nucleotide exchange factor eIF2B","volume":"359","author":"Zyryanova","year":"2018","journal-title":"Science"},{"key":"ref_207","doi-asserted-by":"crossref","first-page":"e1672","DOI":"10.1038\/cddis.2015.49","article-title":"Partial restoration of protein synthesis rates by the small molecule ISRIB prevents neurodegeneration without pancreatic toxicity","volume":"6","author":"Halliday","year":"2015","journal-title":"Cell Death Dis."},{"key":"ref_208","doi-asserted-by":"crossref","first-page":"e62048","DOI":"10.7554\/eLife.62048","article-title":"Small molecule cognitive enhancer reverses age-related memory decline in mice","volume":"9","author":"Krukowski","year":"2020","journal-title":"eLife"},{"key":"ref_209","doi-asserted-by":"crossref","first-page":"4896","DOI":"10.1093\/hmg\/ddx370","article-title":"The role of the ER stress-response protein PERK in rhodopsin retinitis pigmentosa","volume":"26","author":"Athanasiou","year":"2017","journal-title":"Hum. Mol. Genet."},{"key":"ref_210","doi-asserted-by":"crossref","first-page":"e2565","DOI":"10.7717\/peerj.2565","article-title":"A small molecule targeting protein translation does not rescue spatial learning and memory deficits in the hAPP-J20 mouse model of Alzheimer\u2019s disease","volume":"4","author":"Johnson","year":"2016","journal-title":"PeerJ"}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/11\/3\/354\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:29:12Z","timestamp":1760160552000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/11\/3\/354"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,2,26]]},"references-count":210,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2021,3]]}},"alternative-id":["biom11030354"],"URL":"https:\/\/doi.org\/10.3390\/biom11030354","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,2,26]]}}}