{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T16:30:24Z","timestamp":1791304224351,"version":"4.3.1"},"reference-count":94,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2023,2,25]],"date-time":"2023-02-25T00:00:00Z","timestamp":1677283200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Enzyme replacement therapy is the only therapeutic option for Fabry patients with completely absent AGAL activity. However, the treatment has side effects, is costly, and requires conspicuous amounts of recombinant human protein (rh-AGAL). Thus, its optimization would benefit patients and welfare\/health services (i.e., society at large). In this brief report, we describe preliminary results paving the way for two possible approaches: i. the combination of enzyme replacement therapy with pharmacological chaperones; and ii. the identification of AGAL interactors as possible therapeutic targets on which to act. We first showed that galactose, a low-affinity pharmacological chaperone, can prolong AGAL half-life in patient-derived cells treated with rh-AGAL. Then, we analyzed the interactomes of intracellular AGAL on patient-derived AGAL-defective fibroblasts treated with the two rh-AGALs approved for therapeutic purposes and compared the obtained interactomes to the one associated with endogenously produced AGAL (data available as PXD039168 on ProteomeXchange). Common interactors were aggregated and screened for sensitivity to known drugs. Such an interactor-drug list represents a starting point to deeply screen approved drugs and identify those that can affect (positively or negatively) enzyme replacement therapy.<\/jats:p>","DOI":"10.3390\/ijms24054548","type":"journal-article","created":{"date-parts":[[2023,2,27]],"date-time":"2023-02-27T03:23:36Z","timestamp":1677468216000},"page":"4548","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Enzyme Replacement Therapy for FABRY Disease: Possible Strategies to Improve Its Efficacy"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6210-5607","authenticated-orcid":false,"given":"Ilaria","family":"Iacobucci","sequence":"first","affiliation":[{"name":"Department of Chemical Sciences, Universit\u00e0 degli Studi di Napoli \u201cFederico II\u201d, Complesso Universitario Monte Sant\u2019Angelo, Via Cinthia, 80126 Napoli, Italy"},{"name":"CEINGE Biotecnologie Avanzate \u201cFranco Salvatore\u201d, Via G. Salvatore 486, 80131 Napoli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5579-183X","authenticated-orcid":false,"given":"Bruno","family":"Hay Mele","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Napoli \u201cFederico II\u201d, Complesso Universitario Monte Sant\u2019Angelo, Via Cinthia, 80126 Napoli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4648-8107","authenticated-orcid":false,"given":"Flora","family":"Cozzolino","sequence":"additional","affiliation":[{"name":"Department of Chemical Sciences, Universit\u00e0 degli Studi di Napoli \u201cFederico II\u201d, Complesso Universitario Monte Sant\u2019Angelo, Via Cinthia, 80126 Napoli, Italy"},{"name":"CEINGE Biotecnologie Avanzate \u201cFranco Salvatore\u201d, Via G. Salvatore 486, 80131 Napoli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vittoria","family":"Monaco","sequence":"additional","affiliation":[{"name":"Department of Chemical Sciences, Universit\u00e0 degli Studi di Napoli \u201cFederico II\u201d, Complesso Universitario Monte Sant\u2019Angelo, Via Cinthia, 80126 Napoli, Italy"},{"name":"CEINGE Biotecnologie Avanzate \u201cFranco Salvatore\u201d, Via G. Salvatore 486, 80131 Napoli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Cimmaruta","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Napoli \u201cFederico II\u201d, Complesso Universitario Monte Sant\u2019Angelo, Via Cinthia, 80126 Napoli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7775-7154","authenticated-orcid":false,"given":"Maria","family":"Monti","sequence":"additional","affiliation":[{"name":"Department of Chemical Sciences, Universit\u00e0 degli Studi di Napoli \u201cFederico II\u201d, Complesso Universitario Monte Sant\u2019Angelo, Via Cinthia, 80126 Napoli, Italy"},{"name":"CEINGE Biotecnologie Avanzate \u201cFranco Salvatore\u201d, Via G. Salvatore 486, 80131 Napoli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1594-0156","authenticated-orcid":false,"given":"Giuseppina","family":"Andreotti","sequence":"additional","affiliation":[{"name":"Institute of Biomolecular Chemistry ICB, National Research Council (CNR), Via Campi Flegrei 34, 80078 Pozzuoli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3136-2138","authenticated-orcid":false,"given":"Maria","family":"Monticelli","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Napoli \u201cFederico II\u201d, Complesso Universitario Monte Sant\u2019Angelo, Via Cinthia, 80126 Napoli, Italy"},{"name":"Institute of Biomolecular Chemistry ICB, National Research Council (CNR), Via Campi Flegrei 34, 80078 Pozzuoli, Italy"},{"name":"Department of Environmental, Biological, and Pharmaceutical Sciences and Technologies (DiSTABiF), University of Campania \u201cLuigi Vanvitelli\u201d, Via Vivaldi, 43, 81100 Caserta, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Tuttolomondo, A., Simonetta, I., Riolo, R., Todaro, F., Di Chiara, T., Miceli, S., and Pinto, A. (2021). Pathogenesis and Molecular Mechanisms of Anderson\u2013Fabry Disease and Possible New Molecular Addressed Therapeutic Strategies. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms221810088"},{"key":"ref_2","unstructured":"Adam, M.P., Ardinger, H.H., Pagon, R.A., Wallace, S.E., Bean, L.J., Gripp, K.W., Mirzaa, G.M., and Amemiya, A. (1993). GeneReviews\u00ae, University of Washington."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1016\/j.amjms.2020.07.011","article-title":"When and How to Diagnose Fabry Disease in Clinical Pratice","volume":"360","author":"Michaud","year":"2020","journal-title":"Am. J. Med. Sci."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Citro, V., Cammisa, M., Liguori, L., Cimmaruta, C., Lukas, J., Vittoria, M., and Andreotti, G. (2016). The Large Phenotypic Spectrum of Fabry Disease Requires Graduated Diagnosis and Personalized Therapy: A Meta-Analysis Can Help to Differentiate Missense Mutations. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17122010"},{"key":"ref_5","unstructured":"(2022, October 31). ClinVar\u2014Fabry, Available online: https:\/\/www.ncbi.nlm.nih.gov\/clinvar\/?gr=1&term=GLA%5Bgene%5D+AND+Fabry."},{"key":"ref_6","unstructured":"(2022, November 15). Galafold Amenability Table. Available online: https:\/\/galafoldamenabilitytable.com\/reference."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1631","DOI":"10.1681\/ASN.2016090964","article-title":"Characterization of Classical and Nonclassical Fabry Disease: A Multicenter Study","volume":"28","author":"Arends","year":"2017","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1186\/1750-1172-5-30","article-title":"Fabry Disease","volume":"5","author":"Germain","year":"2010","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1016\/j.ymgme.2014.11.005","article-title":"Absence of \u03b1-Galactosidase Cross-Correction in Fabry Heterozygote Cultured Skin Fibroblasts","volume":"114","author":"Fuller","year":"2015","journal-title":"Mol. Genet. Metab."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"874","DOI":"10.1007\/s13311-015-0368-4","article-title":"Effect of Readthrough Treatment in Fibroblasts of Patients Affected by Lysosomal Diseases Caused by Premature Termination Codons","volume":"12","author":"Matalonga","year":"2015","journal-title":"Neurotherapeutics"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"908","DOI":"10.1002\/jimd.12228","article-title":"Developments in the Treatment of Fabry Disease","volume":"43","author":"Hollak","year":"2020","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1016\/j.ekir.2019.11.013","article-title":"Current and Investigational Therapeutics for Fabry Disease","volume":"5","author":"Felis","year":"2019","journal-title":"Kidney Int. Rep."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1080\/15476286.2019.1676115","article-title":"Translational Readthrough of GLA Nonsense Mutations Suggests Dominant-Negative Effects Exerted by the Interaction of Wild-Type and Missense Variants","volume":"17","author":"Lombardi","year":"2019","journal-title":"RNA Biol."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Liguori, L., Monticelli, M., Allocca, M., Mele, B.H., Lukas, J., Cubellis, M.V., and Andreotti, G. (2020). Pharmacological Chaperones: A Therapeutic Approach for Diseases Caused by Destabilizing Missense Mutations. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21020489"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1585","DOI":"10.1006\/bbrc.1993.2659","article-title":"Characterization of a Mutant \u03b1-Galactosidase Gene Product for the Late-Onset Cardiac Form of Fabry Disease","volume":"197","author":"Ishii","year":"1993","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1219","DOI":"10.1006\/bbrc.1995.2416","article-title":"Galactose Stabilizes Various Missense Mutants of \u03b1-Galactosidase in Fabry Disease","volume":"214","author":"Okumiya","year":"1995","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1056\/NEJM200107053450104","article-title":"Improvement in Cardiac Function in the Cardiac Variant of Fabry\u2019s Disease with Galactose-Infusion Therapy","volume":"345","author":"Frustaci","year":"2001","journal-title":"N. Engl. J. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1038\/4801","article-title":"Accelerated Transport and Maturation of Lysosomal \u03b1-Galactosidase A in Fabry Lymphoblasts by an Enzyme Inhibitor","volume":"5","author":"Fan","year":"1999","journal-title":"Nat. Med."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Weidemann, F., Jovanovic, A., Herrmann, K., and Vardarli, I. (2022). Chaperone Therapy in Fabry Disease. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23031887"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1007\/s40265-019-01090-4","article-title":"Migalastat: A Review in Fabry Disease","volume":"79","author":"McCafferty","year":"2019","journal-title":"Drugs"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1007\/s40265-021-01486-1","article-title":"Fabry Disease: The Current Treatment Landscape","volume":"81","author":"Lenders","year":"2021","journal-title":"Drugs"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1093\/glycob\/cwg034","article-title":"A Biochemical and Pharmacological Comparison of Enzyme Replacement Therapies for the Glycolipid Storage Disorder Fabry Disease","volume":"13","author":"Lee","year":"2003","journal-title":"Glycobiology"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1016\/j.ymgme.2014.08.002","article-title":"Characterization of a Chemically Modified Plant Cell Culture Expressed Human \u03b1-Galactosidase-A Enzyme for Treatment of Fabry Disease","volume":"114","author":"Kizhner","year":"2015","journal-title":"Mol. Genet. Metab."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"534","DOI":"10.1002\/jimd.12080","article-title":"Pegunigalsidase Alfa, a Novel PEGylated Enzyme Replacement Therapy for Fabry Disease, Provides Sustained Plasma Concentrations and Favorable Pharmacodynamics: A 1-Year Phase 1\/2 Clinical Trial","volume":"42","author":"Schiffmann","year":"2019","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"S73","DOI":"10.1016\/j.ymgme.2018.12.176","article-title":"Once Every 4 Weeks\u20142 Mg\/Kg of Pegunigalsidase Alfa for Treating Fabry Disease Preliminary Results of a Phase 3 Study","volume":"126","author":"Holida","year":"2019","journal-title":"Mol. Genet. Metab."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1169","DOI":"10.1038\/mt.2015.87","article-title":"Coformulation of a Novel Human \u03b1-Galactosidase a with the Pharmacological Chaperone At1001 Leads to Improved Substrate Reduction in Fabry Mice","volume":"23","author":"Xu","year":"2015","journal-title":"Mol. Ther."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1006\/abbi.2000.1743","article-title":"Role of Ser-65 in the Activity of \u03b1-Galactosidase A: Characterization of a Point Mutation (S65T) Detected in a Patient with Fabry Disease","volume":"377","author":"Ishii","year":"2000","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1521","DOI":"10.1016\/j.chembiol.2011.10.012","article-title":"The Molecular Basis of Pharmacological Chaperoning in Human \u03b1-Galactosidase","volume":"18","author":"Guce","year":"2011","journal-title":"Chem. Biol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1016\/0304-4165(72)90165-1","article-title":"Detection and Properties of an Acid \u03b1-Galactosidase (Ceramidetrihexosidase) in Normal Human Urine","volume":"279","author":"Rietra","year":"1972","journal-title":"BBA Gen. Subj."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1002\/dta.1798","article-title":"Looking for Protein Stabilizing Drugs with Thermal Shift Assay","volume":"7","author":"Andreotti","year":"2015","journal-title":"Drug Test. Anal."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2062","DOI":"10.1016\/S0021-9258(18)61618-7","article-title":"Synthesis and Processing of \u03b1-Galactosidase A in Human Fibroblasts. Evidence for Different Mutations in Fabry Disease","volume":"262","author":"Lemansky","year":"1987","journal-title":"J. Biol. Chem."},{"key":"ref_32","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_33","unstructured":"EMA (2022). Fabrazyme: EPAR\u2014Product Information, EMA (European Medicines Agency)."},{"key":"ref_34","unstructured":"(2022, November 02). DrugBank\u2014Galactose. Available online: https:\/\/go.drugbank.com\/drugs\/DB11735."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Brasil, S., Allocca, M., Magrinho, S.C.M., Santos, I., Raposo, M., Francisco, R., Pascoal, C., Martins, T., Videira, P.A., and Pereira, F. (2022). Systematic Review: Drug Repositioning for Congenital Disorders of Glycosylation (CDG). Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23158725"},{"key":"ref_36","unstructured":"(2022, November 16). Clinical Trials GOV, Available online: https:\/\/clinicaltrials.gov\/."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1263","DOI":"10.1002\/jimd.12406","article-title":"A New D-Galactose Treatment Monitoring Index for PGM1-CDG","volume":"44","author":"Liedtke","year":"2021","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1050","DOI":"10.1016\/j.metabol.2009.02.018","article-title":"Contribution of Galactose and Fructose to Glucose Homeostasis","volume":"58","author":"Sunehag","year":"2009","journal-title":"Metabolism."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Warnock, D.G., Bichet, D.G., Holida, M., Goker-Alpan, O., Nicholls, K., Thomas, M., Eyskens, F., Shankar, S., Adera, M., and Sitaraman, S. (2015). Oral Migalastat HCl Leads to Greater Systemic Exposure and Tissue Levels of Active \u03b1-Galactosidase A in Fabry Patients When Co-Administered with Infused Agalsidase. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0134341"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1042\/BSR20140069","article-title":"Adaptor Protein Complexes and Intracellular Transport","volume":"34","author":"Park","year":"2014","journal-title":"Biosci. Rep."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1742","DOI":"10.1242\/jcs.064170","article-title":"SNX18 Shares a Redundant Role with SNX9 and Modulates Endocytic Trafficking at the Plasma Membrane","volume":"123","author":"Park","year":"2010","journal-title":"J. Cell Sci."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1269","DOI":"10.1242\/jcs.167866","article-title":"Cavin Family Proteins and the Assembly of Caveolae","volume":"128","author":"Kovtun","year":"2015","journal-title":"J. Cell Sci."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1316","DOI":"10.1091\/mbc.e11-09-0787","article-title":"EHD2 Regulates Caveolar Dynamics via ATP-Driven Targeting and Oligomerization","volume":"23","author":"Shah","year":"2012","journal-title":"Mol. Biol. Cell"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/S1937-6448(10)82003-9","article-title":"Lipid Rafts, Caveolae, and Their Endocytosis","volume":"282","author":"Lajoie","year":"2010","journal-title":"Int. Rev. Cell Mol. Biol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2961","DOI":"10.1038\/sj.onc.1209333","article-title":"Involvement of the Rho\/Rac Family Member RhoG in Caveolar Endocytosis","volume":"25","author":"Berenjeno","year":"2006","journal-title":"Oncogene"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1293","DOI":"10.1111\/cas.13259","article-title":"Rho GDP-Dissociation Inhibitor \u03b1 Is a Potential Prognostic Biomarker and Controls Telomere Regulation in Colorectal Cancer","volume":"108","author":"Huang","year":"2017","journal-title":"Cancer Sci."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1136\/jmedgenet-2017-104704","article-title":"Fabry Disease: Characterisation of the Plasma Proteome Pre- and Post-Enzyme Replacement Therapy","volume":"54","author":"Heo","year":"2017","journal-title":"J. Med. Genet."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"e009098","DOI":"10.1161\/JAHA.118.009098","article-title":"Elevated Inflammatory Plasma Biomarkers in Patients with Fabry Disease: A Critical Link to Heart Failure with Preserved Ejection Fraction","volume":"7","author":"Yogasundaram","year":"2018","journal-title":"J. Am. Heart Assoc."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1162","DOI":"10.1039\/c3mb25402j","article-title":"Alteration of Proteomic Profiles in PBMC Isolated from Patients with Fabry Disease: Preliminary Findings","volume":"9","author":"Cigna","year":"2013","journal-title":"Mol. Biosyst."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"137R","DOI":"10.1093\/glycob\/cwl025","article-title":"Galectin-1: A Small Protein with Major Functions","volume":"16","author":"Camby","year":"2006","journal-title":"Glycobiology"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"822","DOI":"10.1111\/tra.12383","article-title":"Structural Basis of Cargo Recognition by Unconventional Myosins in Cellular Trafficking","volume":"17","author":"Li","year":"2016","journal-title":"Traffic"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2310","DOI":"10.4161\/15548627.2014.984272","article-title":"Loss of Functional MYO1C\/Myosin 1c, a Motor Protein Involved in Lipid Raft Trafficking, Disrupts Autophagosome-Lysosome Fusion","volume":"10","author":"Brandstaetter","year":"2014","journal-title":"Autophagy"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"5187304","DOI":"10.1155\/2022\/5187304","article-title":"Myosin 1b Participated in the Modulation of Hypoxia\/Reoxygenation-Caused H9c2 Cell Apoptosis and Autophagy","volume":"2022","author":"Xu","year":"2022","journal-title":"Anal. Cell. Pathol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"719","DOI":"10.4161\/auto.19469","article-title":"Autophagy in Lysosomal Storage Disorders","volume":"8","author":"Lieberman","year":"2012","journal-title":"Autophagy"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1186\/s13046-019-1449-8","article-title":"Downregulation of MYO1C Mediated by Cepharanthine Inhibits Autophagosome-Lysosome Fusion through Blockade of the F-Actin Network","volume":"38","author":"Zhang","year":"2019","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/S0076-6879(07)38002-6","article-title":"Rab8-Optineurin-Myosin VI: Analysis of Interactions and Functions in the Secretory Pathway","volume":"438","author":"Chibalina","year":"2008","journal-title":"Methods Enzymol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1042\/BCJ20190513","article-title":"Proteostasis Regulators Modulate Proteasomal Activity and Gene Expression to Attenuate Multiple Phenotypes in Fabry Disease","volume":"477","author":"Seemann","year":"2020","journal-title":"Biochem. J."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"448","DOI":"10.3389\/fphar.2017.00448","article-title":"Pharmaceutical Chaperones and Proteostasis Regulators in the Therapy of Lysosomal Storage Disorders: Current Perspective and Future Promises","volume":"8","author":"Mohamed","year":"2017","journal-title":"Front. Pharmacol."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Monticelli, M., Hay Mele, B., Allocca, M., Liguori, L., Lukas, J., Monti, M.C., Morretta, E., Cubellis, M.V., and Andreotti, G. (2023). Curcumin Has Beneficial Effects on Lysosomal Alpha-Galactosidase: Potential Implications for the Cure of Fabry Disease. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24021095"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"111385","DOI":"10.1016\/j.fct.2020.111385","article-title":"Curcumin Inhibits Zearalenone-Induced Apoptosis and Oxidative Stress in Leydig Cells via Modulation of the PTEN\/Nrf2\/Bip Signaling Pathway","volume":"141","author":"Chen","year":"2020","journal-title":"Food Chem. Toxicol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"645856","DOI":"10.3389\/fmolb.2021.645856","article-title":"Proteomic Analysis on Anti-Proliferative and Apoptosis Effects of Curcumin Analog, 1,5-Bis(4-Hydroxy-3-Methyoxyphenyl)-1,4-Pentadiene-3-One-Treated Human Glioblastoma and Neuroblastoma Cells","volume":"8","author":"Lee","year":"2021","journal-title":"Front. Mol. Biosci."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"152740","DOI":"10.1016\/j.phymed.2018.11.001","article-title":"Anti-Metastasis Activity of Curcumin against Breast Cancer via the Inhibition of Stem Cell-like Properties and EMT","volume":"58","author":"Hu","year":"2018","journal-title":"Phytomedicine"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1007\/s12282-017-0816-6","article-title":"Investigating the Therapeutic Potential and Mechanism of Curcumin in Breast Cancer Based on RNA Sequencing and Bioinformatics Analysis","volume":"25","author":"Wang","year":"2017","journal-title":"Breast Cancer"},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Lakshmanan, A., Akasov, R.A., Sholina, N.V., Demina, P.A., Generalova, A.N., Gangadharan, A., Sardar, D.K., Lankamsetty, K.B., Khochenkov, D.A., and Khaydukov, E.V. (2021). Nanocurcumin-Loaded UCNPs for Cancer Theranostics: Physicochemical Properties, in Vitro Toxicity, and in Vivo Imaging Studies. Nanomaterials, 11.","DOI":"10.3390\/nano11092234"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1543","DOI":"10.1039\/C4MB00707G","article-title":"Early Markers of Fabry Disease Revealed by Proteomics","volume":"11","author":"Matafora","year":"2015","journal-title":"Mol. Biosyst."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.virol.2016.06.021","article-title":"Vimentin Plays a Role in the Release of the Influenza A Viral Genome from Endosomes","volume":"497","author":"Wu","year":"2016","journal-title":"Virology"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1016\/j.bbamcr.2016.11.020","article-title":"Rab7a Regulates Cell Migration through Rac1 and Vimentin","volume":"1864","author":"Margiotta","year":"2017","journal-title":"Biochim. Biophys. Acta Mol. Cell Res."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1042\/EBC20170055","article-title":"Dysregulation of Autophagy as a Common Mechanism in Lysosomal Storage Diseases","volume":"61","author":"Seranova","year":"2017","journal-title":"Essays Biochem."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1038\/nrd1468","article-title":"Drug Repositioning: Identifying and Developing New Uses for Existing Drugs","volume":"3","author":"Ashburn","year":"2004","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1111\/bph.13798","article-title":"Drug Repurposing from the Perspective of Pharmaceutical Companies","volume":"175","author":"Cha","year":"2017","journal-title":"Br. J. Pharmacol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1038\/534314a","article-title":"Can You Teach Old Drugs New Tricks?","volume":"534","author":"Nosengo","year":"2016","journal-title":"Nature"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"844","DOI":"10.1001\/jama.2020.1166","article-title":"Estimated Research and Development Investment Needed to Bring a New Medicine to Market, 2009-2018","volume":"323","author":"Wouters","year":"2020","journal-title":"JAMA J. Am. Med. Assoc."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1016\/j.apsb.2019.10.003","article-title":"Targeting Autophagy-Related Protein Kinases for Potential Therapeutic Purpose","volume":"10","author":"Xiang","year":"2019","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"222","DOI":"10.7150\/thno.49860","article-title":"Selective Autophagy of Intracellular Organelles: Recent Research Advances","volume":"11","author":"Li","year":"2021","journal-title":"Theranostics"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1016\/j.bulcan.2020.11.004","article-title":"An Overview of Autophagy: Mechanism, Regulation and Research Progress","volume":"108","author":"Cao","year":"2021","journal-title":"Bull. Cancer"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"e108863","DOI":"10.15252\/embj.2021108863","article-title":"Autophagy in Major Human Diseases","volume":"40","author":"Klionsky","year":"2021","journal-title":"EMBO J."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"728","DOI":"10.1016\/j.cell.2011.10.026","article-title":"Autophagy: Renovation of Cells and Tissues","volume":"147","author":"Mizushima","year":"2011","journal-title":"Cell"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/j.bbrc.2022.07.008","article-title":"Novel Protein Kinase CAMP-Activated Catalytic Subunit Alpha (PRKACA) Inhibitor Shows Anti-Tumor Activity in a Fibrolamellar Hepatocellular Carcinoma Model","volume":"621","author":"Toyota","year":"2022","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"5973","DOI":"10.1111\/jcmm.15259","article-title":"Extracellular S100A4 as a Key Player in Fibrotic Diseases","volume":"24","author":"Li","year":"2020","journal-title":"J. Cell. Mol. Med."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1186\/1750-1172-6-66","article-title":"Therapy of Fabry Disease with Pharmacological Chaperones: From in Silico Predictions to in Vitro Tests","volume":"6","author":"Andreotti","year":"2011","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"5032","DOI":"10.1038\/s41598-021-84385-5","article-title":"An Integrated Transcriptomic and Proteomic Approach to Identify the Main Torymus Sinensis Venom Components","volume":"11","author":"Scieuzo","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1175","DOI":"10.1093\/hmg\/ddab047","article-title":"ADAM10 Hyperactivation Acts on Piccolo to Deplete Synaptic Vesicle Stores in Huntington\u2019s Disease","volume":"30","author":"Cozzolino","year":"2021","journal-title":"Hum. Mol. Genet."},{"key":"ref_83","first-page":"D543","article-title":"The PRIDE Database Resources in 2022: A Hub for Mass Spectrometry-Based Proteomics Evidences","volume":"50","author":"Bai","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"975570","DOI":"10.3389\/fmolb.2022.975570","article-title":"Spike S1 Domain Interactome in Non-Pulmonary Systems: A Role beyond the Receptor Recognition","volume":"9","author":"Iacobucci","year":"2022","journal-title":"Front. Mol. Biosci."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1016\/0003-2697(76)90527-3","article-title":"A Rapid and Sensitive Method for the Quantitation of Microgram Quantities of Protein Utilizing the Principle of Protein-Dye Binding","volume":"72","author":"Bradford","year":"1976","journal-title":"Anal. Biochem."},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Citro, V., Pe\u00f1a-Garc\u00eda, J., Den-Haan, H., P\u00e9rez-S\u00e1nchez, H., Del Prete, R., Liguori, L., Cimmaruta, C., Lukas, J., Cubellis, M.V., and Andreotti, G. (2016). Identification of an Allosteric Binding Site on Human Lysosomal Alpha-Galactosidase Opens the Way to New Pharmacological Chaperones for Fabry Disease. PLoS One, 11.","DOI":"10.1371\/journal.pone.0165463"},{"key":"ref_87","unstructured":"R Core Team R Core Team (2021). R A Lang. Environ. Stat. Comput, R Found. Stat. Comput.. Available online: http\/\/www.r-project.org."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1686","DOI":"10.21105\/joss.01686","article-title":"Welcome to the Tidyverse","volume":"4","author":"Wickham","year":"2019","journal-title":"J. Open Source Softw."},{"key":"ref_89","doi-asserted-by":"crossref","unstructured":"Pantoom, S., Hules, L., Sch\u00f6ll, C., Petrosyan, A., Monticelli, M., Pospech, J., Cubellis, M.V., Hermann, A., and Lukas, J. (2022). Mechanistic Insight into the Mode of Action of Acid \u03b2-Glucosidase Enhancer Ambroxol. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23073536"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"e13067","DOI":"10.15252\/emmm.202013067","article-title":"Cysteamine\u2013Bicalutamide Combination Therapy Corrects Proximal Tubule Phenotype in Cystinosis","volume":"13","author":"Jamalpoor","year":"2021","journal-title":"EMBO Mol. Med."},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Holzmann, C., Witt, M., Rolfs, A., Antipova, V., and Wree, A. (2021). Gender-specific Effects of Two Treatment Strategies in a Mouse Model of Niemann-pick Disease Type C1. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22052539"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.coph.2017.04.002","article-title":"Pharmacological Advances for Treatment in Duchenne Muscular Dystrophy","volume":"34","author":"Guiraud","year":"2017","journal-title":"Curr. Opin. Pharmacol."},{"key":"ref_93","first-page":"192","article-title":"Elexacaftor-Tezacaftor-Ivacaftor: The First Triple-Combination Cystic Fibrosis Transmembrane Conductance Regulator Modulating Therapy","volume":"25","author":"Ridley","year":"2020","journal-title":"J. Pediatr. Pharmacol. Ther."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1038\/mt.2011.271","article-title":"Co-Administration with the Pharmacological Chaperone AT1001 Increases Recombinant Human \u03b1-Galactosidase a Tissue Uptake and Improves Substrate Reduction in Fabry Mice","volume":"20","author":"Benjamin","year":"2012","journal-title":"Mol. Ther."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/5\/4548\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:42:39Z","timestamp":1760121759000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/5\/4548"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2,25]]},"references-count":94,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2023,3]]}},"alternative-id":["ijms24054548"],"URL":"https:\/\/doi.org\/10.3390\/ijms24054548","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,2,25]]}}}