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GM2 gangliosidosis, which includes Tay-Sachs and Sandhoff disease, is caused by an accumulation of GM2, mainly in the brain, that leads to progressive neurodegeneration. Previously, we demonstrated in a cellular model of GM2 gangliosidosis that PERK, a UPR sensor, contributes to neuronal death. There is currently no approved treatment for these disorders. Chemical chaperones, such as ursodeoxycholic acid (UDCA), have been found to alleviate ER stress in cell and animal models. UDCA\u2019s ability to move across the blood-brain barrier makes it interesting as a therapeutic tool. Here, we found that UDCA significantly diminished the neurite atrophy induced by GM2 accumulation in primary neuron cultures. It also decreased the up-regulation of pro-apoptotic CHOP, a downstream PERK-signaling component. To explore its potential mechanisms of action, in vitro kinase assays and crosslinking experiments were performed with different variants of recombinant protein PERK, either in solution or in reconstituted liposomes. The results suggest a direct interaction between UDCA and the cytosolic domain of PERK, which promotes kinase phosphorylation and dimerization.<\/jats:p>","DOI":"10.3390\/ijms24087209","type":"journal-article","created":{"date-parts":[[2023,4,14]],"date-time":"2023-04-14T02:28:12Z","timestamp":1681439292000},"page":"7209","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Ursodeoxycholic Acid Binds PERK and Ameliorates Neurite Atrophy in a Cellular Model of GM2 Gangliosidosis"],"prefix":"10.3390","volume":"24","author":[{"given":"Carolina","family":"Morales","sequence":"first","affiliation":[{"name":"Instituto de Investigaci\u00f3n M\u00e9dica M y M Ferreyra, INIMEC-CONICET, Universidad Nacional de C\u00f3rdoba, C\u00f3rdoba 5016, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4060-5146","authenticated-orcid":false,"given":"Macarena","family":"Fernandez","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n M\u00e9dica M y M Ferreyra, INIMEC-CONICET, Universidad Nacional de C\u00f3rdoba, C\u00f3rdoba 5016, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rodrigo","family":"Ferrer","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n M\u00e9dica M y M Ferreyra, INIMEC-CONICET, Universidad Nacional de C\u00f3rdoba, C\u00f3rdoba 5016, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7392-1407","authenticated-orcid":false,"given":"Daniel","family":"Raimunda","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n M\u00e9dica M y M Ferreyra, INIMEC-CONICET, Universidad Nacional de C\u00f3rdoba, C\u00f3rdoba 5016, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dolores C.","family":"Carrer","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n M\u00e9dica M y M Ferreyra, INIMEC-CONICET, Universidad Nacional de C\u00f3rdoba, C\u00f3rdoba 5016, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariana","family":"Bollo","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n M\u00e9dica M y M Ferreyra, INIMEC-CONICET, Universidad Nacional de C\u00f3rdoba, C\u00f3rdoba 5016, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Van Ziel, A.M., and Scheper, W. (2020). The UPR in Neurodegenerative Disease: Not Just an Inside Job. Biomolecules, 10.","DOI":"10.3390\/biom10081090"},{"key":"ref_2","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_3","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1038\/nrneurol.2017.99","article-title":"ER stress and the unfolded protein response in neurodegeneration","volume":"13","author":"Hetz","year":"2017","journal-title":"Nat. Rev. Neurol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"944","DOI":"10.1126\/science.1146361","article-title":"IRE1 signaling affects cell fate during the unfolded protein response","volume":"318","author":"Lin","year":"2007","journal-title":"Science"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Lin, J.H., Li, H., Zhang, Y., Ron, D., and Walter, P. (2009). Divergent effects of PERK and IRE1 signaling on cell viability. PLoS ONE, 4.","DOI":"10.1371\/journal.pone.0004170"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1016\/j.bbamcr.2018.10.014","article-title":"Neurite atrophy and apoptosis mediated by PERK signaling after accumulation of GM2-ganglioside","volume":"1866","author":"Virgolini","year":"2019","journal-title":"Biochim. Biophys. Acta Mol. Cell Res."},{"key":"ref_7","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_8","doi-asserted-by":"crossref","first-page":"7198","DOI":"10.1128\/MCB.23.20.7198-7209.2003","article-title":"Nrf2 is a direct PERK substrate and effector of PERK-dependent cell survival","volume":"23","author":"Cullinan","year":"2003","journal-title":"Mol. Cell. Biol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"20108","DOI":"10.1074\/jbc.M314219200","article-title":"PERK-dependent activation of Nrf2 contributes to redox homeostasis and cell survival following endoplasmic reticulum stress","volume":"279","author":"Cullinan","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1038\/35014014","article-title":"Dynamic interaction of BiP and ER stress transducers in the unfolded-protein response","volume":"2","author":"Bertolotti","year":"2000","journal-title":"Nat. Cell Biol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"14343","DOI":"10.1073\/pnas.0606480103","article-title":"The crystal structure of human IRE1 luminal domain reveals a conserved dimerization interface required for activation of the unfolded protein response","volume":"103","author":"Zhou","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"3028","DOI":"10.1002\/j.1460-2075.1996.tb00666.x","article-title":"Oligomerization and phosphorylation of the Ire1p kinase during intracellular signaling from the endoplasmic reticulum to the nucleus","volume":"15","author":"Shamu","year":"1996","journal-title":"EMBO J."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"4628","DOI":"10.1073\/pnas.1217611110","article-title":"Membrane lipid saturation activates endoplasmic reticulum unfolded protein response transducers through their transmembrane domains","volume":"110","author":"Volmer","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"15920","DOI":"10.1073\/pnas.252341799","article-title":"Control of PERK eIF2alpha kinase activity by the endoplasmic reticulum stress-induced molecular chaperone P58IPK","volume":"99","author":"Yan","year":"2002","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Bollo, M., Paredes, R.M., Holstein, D., Zheleznova, N., Camacho, P., and Lechleiter, J.D. (2010). Calcineurin interacts with PERK and dephosphorylates calnexin to relieve ER stress in mammals and frogs. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0011925"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/j.nbd.2016.06.011","article-title":"Calcineurin beta protects brain after injury by activating the unfolded protein response","volume":"94","author":"Chen","year":"2016","journal-title":"Neurobiol. Dis."},{"key":"ref_17","unstructured":"Gravel, R., Kaback, M., Proia, R., Sandhoff, K., Suzuki, K., and Suzuki, K. (2000). The Metabolic and Molecular Bases of Inherited Disease, McGraw-Hill."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"10195","DOI":"10.1523\/JNEUROSCI.0822-13.2013","article-title":"Gangliosides and gangliosidoses: Principles of molecular and metabolic pathogenesis","volume":"33","author":"Sandhoff","year":"2013","journal-title":"J. Neurosci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"111","DOI":"10.2147\/TACG.S85354","article-title":"Animal models of GM2 gangliosidosis: Utility and limitations","volume":"9","author":"Lawson","year":"2016","journal-title":"Appl. Clin. Genet."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1379\/1466-1268(1996)001<0109:IOMACC>2.3.CO;2","article-title":"Influence of molecular and chemical chaperones on protein folding","volume":"1","author":"Welch","year":"1996","journal-title":"Cell Stress Chaperones"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1016\/j.bbrc.2011.05.043","article-title":"Structure-function analysis of the tertiary bile acid TUDCA for the resolution of endoplasmic reticulum stress in intestinal epithelial cells","volume":"409","author":"Berger","year":"2011","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1007\/s12192-011-0259-5","article-title":"Cholesterol-derived bile acids enhance the chaperone activity of alpha-crystallins","volume":"16","author":"Song","year":"2011","journal-title":"Cell Stress Chaperones"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"592","DOI":"10.1053\/jhep.2002.35441","article-title":"Effect of tauroursodeoxycholic acid on endoplasmic reticulum stress-induced caspase-12 activation","volume":"36","author":"Xie","year":"2002","journal-title":"Hepatology"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1038\/labinvest.2016.44","article-title":"Ursodeoxycholic acid and 4-phenylbutyrate prevent endoplasmic reticulum stress-induced podocyte apoptosis in diabetic nephropathy","volume":"96","author":"Cao","year":"2016","journal-title":"Lab. Investig."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1016\/j.bbrc.2011.08.080","article-title":"Protective effect of catechin in type I Gaucher disease cells by reducing endoplasmic reticulum stress","volume":"413","author":"Lee","year":"2011","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Monticelli, M., Liguori, L., Allocca, M., Bosso, A., Andreotti, G., Lukas, J., Monti, M.C., Morretta, E., Cubellis, M.V., and Hay Mele, B. (2022). Drug Repositioning for Fabry Disease: Acetylsalicylic Acid Potentiates the Stabilization of Lysosomal Alpha-Galactosidase by Pharmacological Chaperones. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23095105"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1093\/hmg\/ddm324","article-title":"ER and oxidative stresses are common mediators of apoptosis in both neurodegenerative and non-neurodegenerative lysosomal storage disorders and are alleviated by chemical chaperones","volume":"17","author":"Wei","year":"2008","journal-title":"Hum. Mol. Genet."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1523\/JNEUROSCI.10-01-00293.1990","article-title":"Ganglioside-enhanced neurite growth: Evidence for a selective induction of high-molecular-weight MAP-2","volume":"10","author":"Ferreira","year":"1990","journal-title":"J. Neurosci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1094","DOI":"10.1007\/s00018-009-8746-x","article-title":"Tauroursodeoxycholic acid prevents E22Q Alzheimer\u2019s Abeta toxicity in human cerebral endothelial cells","volume":"66","author":"Viana","year":"2009","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.abb.2014.12.031","article-title":"Tauroursodeoxycholic acid prevents stress induced aggregation of proteins in vitro and promotes PERK activation in HepG2 cells","volume":"568","author":"Gani","year":"2015","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"G773","DOI":"10.1152\/ajpgi.00483.2010","article-title":"Tauroursodeoxycholic acid reduces endoplasmic reticulum stress, acinar cell damage, and systemic inflammation in acute pancreatitis","volume":"301","author":"Seyhun","year":"2011","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"602","DOI":"10.1038\/385602a0","article-title":"Crystal structure of the Src family tyrosine kinase Hck","volume":"385","author":"Sicheri","year":"1997","journal-title":"Nature"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1016\/j.cell.2005.06.044","article-title":"Higher-order substrate recognition of eIF2alpha by the RNA-dependent protein kinase PKR","volume":"122","author":"Dar","year":"2005","journal-title":"Cell"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1107\/S0907444911006445","article-title":"The structure of the PERK kinase domain suggests the mechanism for its activation","volume":"67","author":"Cui","year":"2011","journal-title":"Acta Crystallogr. D Biol. Crystallogr."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1083\/jcb.200508099","article-title":"Activation-dependent substrate recruitment by the eukaryotic translation initiation factor 2 kinase PERK","volume":"172","author":"Marciniak","year":"2006","journal-title":"J. Cell Biol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1042\/bj3460281","article-title":"Pancreatic eukaryotic initiation factor-2alpha kinase (PEK) homologues in humans, Drosophila melanogaster and Caenorhabditis elegans that mediate translational control in response to endoplasmic reticulum stress","volume":"346","author":"Sood","year":"2000","journal-title":"Biochem. J."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1146\/annurev-cellbio-101011-155826","article-title":"Structural basis of the unfolded protein response","volume":"28","author":"Korennykh","year":"2012","journal-title":"Annu. Rev. Cell Dev. Biol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1038\/nature07661","article-title":"The unfolded protein response signals through high-order assembly of Ire1","volume":"457","author":"Korennykh","year":"2009","journal-title":"Nature"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1137","DOI":"10.1016\/j.cell.2006.05.013","article-title":"An allosteric mechanism for activation of the kinase domain of epidermal growth factor receptor","volume":"125","author":"Zhang","year":"2006","journal-title":"Cell"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1137","DOI":"10.1126\/science.1128294","article-title":"Chemical chaperones reduce ER stress and restore glucose homeostasis in a mouse model of type 2 diabetes","volume":"313","author":"Ozcan","year":"2006","journal-title":"Science"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"27905","DOI":"10.1074\/jbc.M702672200","article-title":"Chemical chaperones reduce endoplasmic reticulum stress and prevent mutant HFE aggregate formation","volume":"282","author":"Picarote","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Xie, W., Pariollaud, M., Wixted, W.E., Chitnis, N., Fornwald, J., Truong, M., Pao, C., Liu, Y., Ames, R.S., and Callahan, J. (2015). Identification and characterization of PERK activators by phenotypic screening and their effects on NRF2 activation. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0119738"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1038\/nrm2330","article-title":"Membrane lipids: Where they are and how they behave","volume":"9","author":"Voelker","year":"2008","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"29496","DOI":"10.1074\/jbc.M302964200","article-title":"Inhibition of calcium uptake via the sarco\/endoplasmic reticulum Ca2+-ATPase in a mouse model of Sandhoff disease and prevention by treatment with N-butyldeoxynojirimycin","volume":"278","author":"Pelled","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1905","DOI":"10.15252\/embr.201643426","article-title":"The ins and outs of endoplasmic reticulum-controlled lipid biosynthesis","volume":"18","author":"Jacquemyn","year":"2017","journal-title":"EMBO Rep."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"886","DOI":"10.1016\/j.devcel.2012.10.009","article-title":"Curvature, lipid packing, and electrostatics of membrane organelles: Defining cellular territories in determining specificity","volume":"23","author":"Bigay","year":"2012","journal-title":"Dev. Cell"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"688","DOI":"10.1016\/j.bbamem.2009.12.027","article-title":"Liquid-ordered phases induced by cholesterol: A compendium of binary phase diagrams","volume":"1798","author":"Marsh","year":"2010","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1016\/j.bbamem.2008.11.010","article-title":"How the molecular features of glycosphingolipids affect domain formation in fluid membranes","volume":"1788","author":"Westerlund","year":"2009","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.chemphyslip.2005.10.003","article-title":"Behavior of GM3 ganglioside in lipid monolayers mimicking rafts or fluid phase in membranes","volume":"139","author":"Turlet","year":"2006","journal-title":"Chem. Phys. Lipids"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"10477","DOI":"10.1021\/bi00200a032","article-title":"Long- and short-range interactions between phospholipid\/ganglioside GM1 bilayers","volume":"33","author":"McIntosh","year":"1994","journal-title":"Biochemistry"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1545","DOI":"10.1016\/j.bbamem.2008.01.015","article-title":"Protein modulation of lipids, and vice-versa, in membranes","volume":"1778","author":"Marsh","year":"2008","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"24881","DOI":"10.1074\/jbc.M004454200","article-title":"Ligand-independent dimerization activates the stress response kinases IRE1 and PERK in the lumen of the endoplasmic reticulum","volume":"275","author":"Liu","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_53","first-page":"e61974","article-title":"Molecular Modulation by Lentivirus-Delivered Specific shRNAs in Endoplasmic Reticulum Stressed Neurons","volume":"170","author":"Morales","year":"2021","journal-title":"J. Vis. Exp."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"729513","DOI":"10.3389\/fmolb.2021.729513","article-title":"Structural Biology in the Clouds: The WeNMR-EOSC Ecosystem","volume":"8","author":"Honorato","year":"2021","journal-title":"Front. Mol. Biosci."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"10161","DOI":"10.1021\/bi010919a","article-title":"Crystal structure of human type III 3alpha-hydroxysteroid dehydrogenase\/bile acid binding protein complexed with NADP(+) and ursodeoxycholate","volume":"40","author":"Jin","year":"2001","journal-title":"Biochemistry"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1605","DOI":"10.1002\/jcc.20084","article-title":"UCSF Chimera--a visualization system for exploratory research and analysis","volume":"25","author":"Pettersen","year":"2004","journal-title":"J. Comput. Chem."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/8\/7209\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:15:33Z","timestamp":1760123733000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/8\/7209"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,4,13]]},"references-count":56,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2023,4]]}},"alternative-id":["ijms24087209"],"URL":"https:\/\/doi.org\/10.3390\/ijms24087209","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,4,13]]}}}