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The lysosomal enzyme beta-glucocerebrosidase (GCase) encoded by the GBA1 gene participates in both the endolysosomal pathway and the immune response. Disruption of these mechanisms is involved in PD pathogenesis. However, molecular mechanisms of PD associated with GBA1 mutations (GBA-PD) are unknown today in particular due to the partial penetrance of GBA1 variants in PD. The modifiers of GBA1 penetrance have not been elucidated. We characterized the transcriptomic profiles of cells from the substantia nigra (SN) of mice with co-injection with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and selective inhibitor of GCase activity (conduritol-\u03b2-epoxide, (CBE)) to mimic PD bearing GCase dysfunction (MPTP+CBE), mice treated with MPTP, mice treated with CBE and control mice treated with injection of sodium chloride (NaCl) (vehicle). Differential expression analysis, pathway enrichment analysis, and outlier detection were performed. Functional clustering of differentially represented transcripts revealed more processes associated with the functioning of neurogenesis, inflammation, apoptosis and autophagy in MPTP+CBE and MPTP mice than in vehicle mice, with a more pronounced alteration of autophagy processes in MPTP+CBE mice than in MPTP mice. The PI3K-Akt-mTOR signaling pathway may be considered a potential target for therapy in PD with GCase dysfunction.<\/jats:p>","DOI":"10.3390\/ijms241512164","type":"journal-article","created":{"date-parts":[[2023,7,31]],"date-time":"2023-07-31T01:26:40Z","timestamp":1690766800000},"page":"12164","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Whole Transcriptome Analysis of Substantia Nigra in Mice with MPTP-Induced Parkinsonism Bearing Defective Glucocerebrosidase Activity"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5132-2283","authenticated-orcid":false,"given":"Tatiana","family":"Usenko","sequence":"first","affiliation":[{"name":"Petersburg Nuclear Physics Institute Named by B.P. Konstantinov of National Research Centre \u00abKurchatov Institute\u00bb, 188300 Gatchina, Russia"},{"name":"Department of Molecular Genetic and Nanobiological Technologies, Pavlov First Saint-Petersburg State Medical University, 197022 Saint-Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anastasia","family":"Bezrukova","sequence":"additional","affiliation":[{"name":"Petersburg Nuclear Physics Institute Named by B.P. Konstantinov of National Research Centre \u00abKurchatov Institute\u00bb, 188300 Gatchina, Russia"},{"name":"Department of Molecular Genetic and Nanobiological Technologies, Pavlov First Saint-Petersburg State Medical University, 197022 Saint-Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margarita M.","family":"Rudenok","sequence":"additional","affiliation":[{"name":"Institute of Molecular Genetics, Russian Academy of Sciences, 123182 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katerina","family":"Basharova","sequence":"additional","affiliation":[{"name":"Petersburg Nuclear Physics Institute Named by B.P. Konstantinov of National Research Centre \u00abKurchatov Institute\u00bb, 188300 Gatchina, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria I.","family":"Shadrina","sequence":"additional","affiliation":[{"name":"Institute of Molecular Genetics, Russian Academy of Sciences, 123182 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petr A.","family":"Slominsky","sequence":"additional","affiliation":[{"name":"Institute of Molecular Genetics, Russian Academy of Sciences, 123182 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ekaterina","family":"Zakharova","sequence":"additional","affiliation":[{"name":"Research Center for Medical Genetics, Laboratory of Hereditary Metabolic Diseases, 115522 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sofya","family":"Pchelina","sequence":"additional","affiliation":[{"name":"Petersburg Nuclear Physics Institute Named by B.P. Konstantinov of National Research Centre \u00abKurchatov Institute\u00bb, 188300 Gatchina, Russia"},{"name":"Department of Molecular Genetic and Nanobiological Technologies, Pavlov First Saint-Petersburg State Medical University, 197022 Saint-Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,7,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.neuron.2006.09.026","article-title":"Mechanisms of Parkinson\u2019s Disease Linked to Pathological \u03b1-Synuclein: New Targets for Drug Discovery","volume":"52","author":"Lee","year":"2006","journal-title":"Neuron"},{"key":"ref_2","first-page":"1720621","article-title":"Alpha-Synuclein in Parkinson\u2019s Disease: From Pathogenetic Dysfunction to Potential Clinical Application","volume":"2016","author":"Xu","year":"2016","journal-title":"Park. Dis."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2277","DOI":"10.1212\/01.wnl.0000304039.11891.29","article-title":"Genotype-Phenotype Correlations between GBA Mutations and Parkinson Disease Risk and Onset","volume":"70","author":"Giladi","year":"2008","journal-title":"Neurology"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1093\/hmg\/ddq454","article-title":"Large-Scale Screening of the Gaucher\u2019s Disease-Related Glucocerebrosidase Gene in Europeans with Parkinson\u2019s Disease","volume":"20","author":"Lesage","year":"2011","journal-title":"Hum. Mol. Genet."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"935.e3","DOI":"10.1016\/j.neurobiolaging.2013.09.019","article-title":"Clinicogenetic Study of GBA Mutations in Patients with Familial Parkinson\u2019s Disease","volume":"35","author":"Li","year":"2014","journal-title":"Neurobiol. Aging"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1651","DOI":"10.1056\/NEJMoa0901281","article-title":"Multicenter Analysis of Glucocerebrosidase Mutations in Parkinson\u2019s Disease","volume":"361","author":"Sidransky","year":"2009","journal-title":"N. Engl. J. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"267.e7","DOI":"10.1016\/j.neurobiolaging.2018.06.027","article-title":"Mutation Analysis of Parkinson\u2019s Disease Genes in a Russian Data Set","volume":"71","author":"Emelyanov","year":"2018","journal-title":"Neurobiol. Aging"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"240ra73","DOI":"10.1126\/scitranslmed.3008659","article-title":"Macrophage Models of Gaucher Disease for Evaluating Disease Pathogenesis and Candidate Drugs","volume":"6","author":"Aflaki","year":"2014","journal-title":"Sci. Transl. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"105014","DOI":"10.1016\/j.nbd.2020.105014","article-title":"Ceramide Signalling in Inherited and Multifactorial Brain Metabolic Diseases","volume":"143","author":"Pant","year":"2020","journal-title":"Neurobiol. Dis."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Lai, M., La Rocca, V., Amato, R., Freer, G., and Pistello, M. (2019). Sphingolipid\/Ceramide Pathways and Autophagy in the Onset and Progression of Melanoma: Novel Therapeutic Targets and Opportunities. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20143436"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Honn, K.V., and Zeldin, D.C. (2019). The Role of Bioactive Lipids in Cancer, Inflammation and Related Diseases, Springer International Publishing.","DOI":"10.1007\/978-3-030-21735-8"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Usenko, T., Bezrukova, A., Basharova, K., Panteleeva, A., Nikolaev, M., Kopytova, A., Miliukhina, I., Emelyanov, A., Zakharova, E., and Pchelina, S. (2021). Comparative Transcriptome Analysis in Monocyte-Derived Macrophages of Asymptomatic GBA Mutation Carriers and Patients with GBA-Associated Parkinson\u2019s Disease. Genes, 12.","DOI":"10.3390\/genes12101545"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2648","DOI":"10.1093\/brain\/awv179","article-title":"Glucocerebrosidase Activity in Parkinson\u2019s Disease with and without GBA Mutations","volume":"138","author":"Alcalay","year":"2015","journal-title":"Brain"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.parkreldis.2017.08.026","article-title":"Serum Lipid Alterations in GBA-Associated Parkinson\u2019s Disease","volume":"44","author":"Guedes","year":"2017","journal-title":"Park. Relat. Disord."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/j.neulet.2016.10.039","article-title":"Oligomeric \u03b1-Synuclein and Glucocerebrosidase Activity Levels in GBA-Associated Parkinson\u2019s Disease","volume":"636","author":"Pchelina","year":"2017","journal-title":"Neurosci. Lett."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1325","DOI":"10.1002\/mds.27393","article-title":"Blood Lysosphingolipids Accumulation in Patients with Parkinson\u2019s Disease with Glucocerebrosidase 1 Mutations","volume":"33","author":"Pchelina","year":"2018","journal-title":"Mov. Disord."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1779","DOI":"10.1002\/mds.29132","article-title":"Could Blood Hexosylsphingosine Be a Marker for Parkinson\u2019s Disease Linked with GBA1 Mutations?","volume":"37","author":"Kopytova","year":"2022","journal-title":"Mov. Disord."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1126\/science.6823561","article-title":"Chronic Parkinsonism in Humans Due to a Product of Meperidine-Analog Synthesis","volume":"219","author":"Langston","year":"1983","journal-title":"Science"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1111\/jnc.13409","article-title":"Chronic and Progressive Parkinson\u2019s Disease MPTP Model in Adult and Aged Mice","volume":"136","author":"Villadiego","year":"2016","journal-title":"J. Neurochem."},{"key":"ref_20","first-page":"422","article-title":"MPTP-Induced Mouse Model of Parkinson\u2019s Disease: A Promising Direction of Therapeutic Strategies","volume":"21","author":"Mustapha","year":"2021","journal-title":"Biomol. Biomed."},{"key":"ref_21","first-page":"19","article-title":"MPTP Mouse Models of Parkinson\u2019s Disease: An Update","volume":"1","author":"Meredith","year":"2011","journal-title":"J. Park. Dis."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/0006-291X(75)90286-7","article-title":"The Gaucher Mouse","volume":"67","author":"Kanfer","year":"1975","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1016\/j.nbd.2018.12.001","article-title":"Development and Biochemical Characterization of a Mouse Model of Parkinson\u2019s Disease Bearing Defective Glucocerebrosidase Activity","volume":"124","author":"Mus","year":"2019","journal-title":"Neurobiol. Dis."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/j.neuroscience.2011.03.007","article-title":"Modeling of Presymptomatic and Symptomatic Stages of Parkinsonism in Mice","volume":"181","author":"Ugrumov","year":"2011","journal-title":"Neuroscience"},{"key":"ref_25","unstructured":"Pchelina, S.N., Bezrukova, A.I., Rudenok, M.M., Zhuravlev, A.S., Rybolovlev, I.N., Baydakova, G.V., Nikolaev, M.A., Nesterov, M.S., Abaimov, D.A., and Usenko, T.S. (2023). Biochemical characterization of double toxic MPTP\/CBE presymptomatic Parkison like phenotype in mice. NeuroToxicology, submitted."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1093\/nar\/30.1.207","article-title":"Gene Expression Omnibus: NCBI Gene Expression and Hybridization Array Data Repository","volume":"30","author":"Edgar","year":"2002","journal-title":"Nucleic Acids Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"6775","DOI":"10.1007\/s12035-016-0190-y","article-title":"Transcriptome Profile Changes in Mice with MPTP-Induced Early Stages of Parkinson\u2019s Disease","volume":"54","author":"Alieva","year":"2017","journal-title":"Mol. Neurobiol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"7229","DOI":"10.1007\/s12035-018-0907-1","article-title":"Whole-Transcriptome Analysis of Mouse Models with MPTP-Induced Early Stages of Parkinson\u2019s Disease Reveals Stage-Specific Response of Transcriptome and a Possible Role of Myelin-Linked Genes in Neurodegeneration","volume":"55","author":"Alieva","year":"2018","journal-title":"Mol. Neurobiol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1002\/path.4751","article-title":"Delineating Pathological Pathways in a Chemically Induced Mouse Model of Gaucher Disease","volume":"239","author":"Vardi","year":"2016","journal-title":"J. Pathol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1186\/s12974-020-01934-x","article-title":"Mice Defective in Interferon Signaling Help Distinguish between Primary and Secondary Pathological Pathways in a Mouse Model of Neuronal Forms of Gaucher Disease","volume":"17","author":"Vardi","year":"2020","journal-title":"J. Neuroinflammation"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Xu, Y.-H., Jia, L., Quinn, B., Zamzow, M., Stringer, K., Aronow, B., Sun, Y., Zhang, W., Setchell, K.D.R., and Grabowski, G.A. (2011). Global Gene Expression Profile Progression in Gaucher Disease Mouse Models. BMC Genom., 12.","DOI":"10.1186\/1471-2164-12-20"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"e79830","DOI":"10.7554\/eLife.79830","article-title":"Neuroinflammation in Neuronopathic Gaucher Disease: Role of Microglia and NK Cells, Biomarkers, and Response to Substrate Reduction Therapy","volume":"11","author":"Boddupalli","year":"2022","journal-title":"Elife"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1186\/1743-7075-4-18","article-title":"The Role of Proopiomelanocortin (POMC) Neurones in Feeding Behaviour","volume":"4","author":"Millington","year":"2007","journal-title":"Nutr. Metab."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1186\/s13024-022-00554-8","article-title":"Transcriptome Deregulation of Peripheral Monocytes and Whole Blood in GBA-Related Parkinson\u2019s Disease","volume":"17","author":"Riboldi","year":"2022","journal-title":"Mol. Neurodegener."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1016\/j.neuro.2021.10.008","article-title":"Are Ion Channels Potential Therapeutic Targets for Parkinson\u2019s Disease?","volume":"87","author":"Daniel","year":"2021","journal-title":"Neurotoxicology"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1038\/s41531-022-00324-9","article-title":"Altered Neural Cell Junctions and Ion-Channels Leading to Disrupted Neuron Communication in Parkinson\u2019s Disease","volume":"8","author":"Choudhury","year":"2022","journal-title":"NPJ Park. Dis."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1007\/s10517-020-04723-x","article-title":"Plasma Cytokines Profile in Patients with Parkinson\u2019s Disease Associated with Mutations in GBA Gene","volume":"168","author":"Miliukhina","year":"2020","journal-title":"Bull. Exp. Biol. Med."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1038\/nature21368","article-title":"Complement Drives Glucosylceramide Accumulation and Tissue Inflammation in Gaucher Disease","volume":"543","author":"Pandey","year":"2017","journal-title":"Nature"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"E3285","DOI":"10.1073\/pnas.1618133114","article-title":"Intracellular Metabolite \u03b2-Glucosylceramide Is an Endogenous Mincle Ligand Possessing Immunostimulatory Activity","volume":"114","author":"Nagata","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.mrfmmm.2004.06.056","article-title":"ER Stress and the Unfolded Protein Response","volume":"569","author":"Kaufman","year":"2005","journal-title":"Mutat. Res. Fundam. Mol. Mech. Mutagen."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"239854","DOI":"10.1155\/2013\/239854","article-title":"Endoplasmic Reticulum Stress and Parkinson\u2019s Disease: The Role of HRD1 in Averting Apoptosis in Neurodegenerative Disease","volume":"2013","author":"Omura","year":"2013","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"da Costa, C.A., El Manaa, W., Duplan, E., and Checler, F. (2020). The Endoplasmic Reticulum Stress\/Unfolded Protein Response and Their Contributions to Parkinson\u2019s Disease Physiopathology. Cells, 9.","DOI":"10.3390\/cells9112495"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Smith, L., and Schapira, A.H. (2022). GBA Variants and Parkinson Disease: Mechanisms and Treatments. Cells, 11.","DOI":"10.3390\/cells11081261"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1186\/1750-1172-8-140","article-title":"Unfolded Protein Response in Gaucher Disease: From Human to Drosophila","volume":"8","author":"Maor","year":"2013","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1111\/j.1471-4159.2012.07879.x","article-title":"Glucocerebrosidase Mutations Alter the Endoplasmic Reticulum and Lysosomes in Lewy Body Disease","volume":"123","author":"Hanson","year":"2012","journal-title":"J. Neurochem."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"4028","DOI":"10.1038\/ncomms5028","article-title":"IPSC-Derived Neurons from GBA1-Associated Parkinson\u2019s Disease Patients Show Autophagic Defects and Impaired Calcium Homeostasis","volume":"5","author":"Aureli","year":"2014","journal-title":"Nat. Commun."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"31380","DOI":"10.1038\/srep31380","article-title":"Parkinson Disease-Linked GBA Mutation Effects Reversed by Molecular Chaperones in Human Cell and Fly Models","volume":"6","author":"Beavan","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1016\/j.stemcr.2016.01.013","article-title":"ER Stress and Autophagic Perturbations Lead to Elevated Extracellular \u03b1-Synuclein in GBA-N370S Parkinson\u2019s IPSC-Derived Dopamine Neurons","volume":"6","author":"Fernandes","year":"2016","journal-title":"Stem Cell Rep."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"eabm6393","DOI":"10.1126\/sciadv.abm6393","article-title":"Mutant Glucocerebrosidase Impairs \u03b1-Synuclein Degradation by Blockade of Chaperone-Mediated Autophagy","volume":"8","author":"Kuo","year":"2022","journal-title":"Sci. Adv."},{"key":"ref_50","first-page":"43","article-title":"Gene Expression of Lysosomal Membrane Proteins in Parkinson Disease, Associated with Mutations in the Glucocerebrosidase Gene (Gba)","volume":"14","author":"Usenko","year":"2020","journal-title":"Ann. Clin. Exp. Neurol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"2694","DOI":"10.1016\/j.cellsig.2014.08.019","article-title":"The Role of PI3K\/AKT\/MTOR Pathway in the Modulation of Autophagy and the Clearance of Protein Aggregates in Neurodegeneration","volume":"26","year":"2014","journal-title":"Cell Signal."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1186\/s13578-020-00416-0","article-title":"RETRACTED ARTICLE: Roles of the PI3K\/AKT\/MTOR Signalling Pathways in Neurodegenerative Diseases and Tumours","volume":"10","author":"Xu","year":"2020","journal-title":"Cell Biosci."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1142\/S0192415X19500277","article-title":"Acupuncture Inhibits the Increase in Alpha-Synuclein by Modulating SGK1 in an MPTP Induced Parkinsonism Mouse Model","volume":"47","author":"Yeo","year":"2019","journal-title":"Am. J. Chin. Med."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1089\/ars.2021.0083","article-title":"PDK4 Decrease Neuronal Apoptosis via Inhibiting ROS-ASK1\/P38 Pathway in Early Brain Injury after Subarachnoid Hemorrhage","volume":"36","author":"Gao","year":"2021","journal-title":"Antioxid. Redox Signal."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Gao, X., Gao, Y.-Y., Wu, L.-Y., Peng, Z., Liu, X.-Z., Chen, X.-X., Gao, S., Zhang, H.-S., Lu, Y., and Hang, C.-H. (2022). High Expression of PDK4 Could Play a Potentially Protective Role by Attenuating Oxidative Stress after Subarachnoid Hemorrhage. J. Clin. Med., 11.","DOI":"10.3390\/jcm11143974"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1159\/000493228","article-title":"Lentiviral Vector-Mediated SHC3 Silencing Exacerbates Oxidative Stress Injury in Nigral Dopamine Neurons by Regulating the PI3K-AKT-FoxO Signaling Pathway in Rats with Parkinson\u2019s Disease","volume":"49","author":"Gong","year":"2018","journal-title":"Cell Physiol. Biochem."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1016\/j.ccell.2016.06.004","article-title":"PDK1-SGK1 Signaling Sustains AKT-Independent MTORC1 Activation and Confers Resistance to PI3K\u03b1 Inhibition","volume":"30","author":"Castel","year":"2016","journal-title":"Cancer Cell"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"29739","DOI":"10.1074\/jbc.M114.584821","article-title":"PDK4 Promotes Tumorigenesis Through Activation of CREB-RHEB-MTORC1 Signaling Cascade","volume":"289","author":"Liu","year":"2014","journal-title":"J. Biol. Chem."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"616","DOI":"10.1038\/s41419-021-03899-y","article-title":"RTP801\/REDD1 Contributes to Neuroinflammation Severity and Memory Impairments in Alzheimer\u2019s Disease","volume":"12","author":"Mandelkow","year":"2021","journal-title":"Cell Death Dis."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1097\/BS9.0000000000000069","article-title":"DDIT4 Mediates the Proliferation-Promotive Effect of IL-34 in Human Monocytic Leukemia Cells","volume":"3","author":"Lv","year":"2021","journal-title":"Blood Sci."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"9996","DOI":"10.1523\/JNEUROSCI.3292-06.2006","article-title":"RTP801 Is Elevated in Parkinson Brain Substantia Nigral Neurons and Mediates Death in Cellular Models of Parkinson\u2019s Disease by a Mechanism Involving Mammalian Target of Rapamycin Inactivation","volume":"26","author":"Malagelada","year":"2006","journal-title":"J. Neurosci."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1007\/s00702-023-02604-x","article-title":"Genes Critical for Development and Differentiation of Dopaminergic Neurons Are Downregulated in Parkinson\u2019s Disease","volume":"130","author":"Verma","year":"2023","journal-title":"J. Neural. Transm."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Li, C.C., Wu, T.S., Huang, C.F., Jang, L.T., Liu, Y.T., You, S.T., Liou, G.G., and Lee, F.J.S. (2012). GTP-Binding-Defective ARL4D Alters Mitochondrial Morphology and Membrane Potential. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0043552"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1002\/path.5189","article-title":"ARL4C Stabilized by AKT\/MTOR Pathway Promotes the Invasion of PTEN-Deficient Primary Human Glioblastoma","volume":"247","author":"Chen","year":"2019","journal-title":"J. Pathol."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Dong, R., Li, X., and Lai, K.O. (2021). Activity and Function of the Prmt8 Protein Arginine Methyltransferase in Neurons. Life, 11.","DOI":"10.3390\/life11111132"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"112180","DOI":"10.1016\/j.celrep.2023.112180","article-title":"Post-Translational Proteomics Platform Identifies Neurite Outgrowth Impairments in Parkinson\u2019s Disease GBA-N370S Dopamine Neurons","volume":"42","author":"Bogetofte","year":"2023","journal-title":"Cell Rep."},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Grigor\u2019eva, E.V., Kopytova, A.E., Yarkova, E.S., Pavlova, S.V., Sorogina, D.A., Malakhova, A.A., Malankhanova, T.B., Baydakova, G.V., Zakharova, E.Y., and Medvedev, S.P. (2023). Biochemical Characteristics of IPSC-Derived Dopaminergic Neurons from N370S GBA Variant Carriers with and without Parkinson\u2019s Disease. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24054437"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1152503","DOI":"10.3389\/fnins.2023.1152503","article-title":"Deregulation of MTORC1-TFEB Axis in Human IPSC Model of GBA1-Associated Parkinson\u2019s Disease","volume":"17","author":"Mubariz","year":"2023","journal-title":"Front. Neurosci."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"2111","DOI":"10.1002\/mds.28200","article-title":"Penetrance of Glucocerebrosidase (GBA) Mutations in Parkinson\u2019s Disease: A Kin Cohort Study","volume":"35","author":"Balestrino","year":"2020","journal-title":"Mov. Disord."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1443","DOI":"10.1080\/15548627.2015.1067364","article-title":"Genetic Perspective on the Role of the Autophagy-Lysosome Pathway in Parkinson Disease","volume":"11","author":"Dion","year":"2015","journal-title":"Autophagy"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"380","DOI":"10.4103\/1673-5374.202934","article-title":"The Emerging Role of Autophagic-Lysosomal Dysfunction in Gaucher Disease and Parkinson\u2019s Disease","volume":"12","author":"Kinghorn","year":"2017","journal-title":"Neural Regen. Res."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1397","DOI":"10.2147\/NDT.S299810","article-title":"Mechanism of Autophagy Regulation in MPTP-Induced PD Mice via the MTOR Signaling Pathway by Echinacoside","volume":"17","author":"Zhang","year":"2021","journal-title":"Neuropsychiatr. Dis. Treat."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"E734","DOI":"10.1152\/ajpendo.00071.2020","article-title":"IGF-1 Inhibits MPTP\/MPP +-Induced Autophagy on Dopaminergic Neurons through the IGF-1R\/PI3K-Akt-MTOR Pathway and GPER","volume":"319","author":"Wang","year":"2020","journal-title":"Am. J. Physiol.-Endocrinol. Metab."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"8366","DOI":"10.1039\/D1FO01360B","article-title":"Protective Effects of Berberine against MPTP-Induced Dopaminergic Neuron Injury through Promoting Autophagy in Mice","volume":"12","author":"Deng","year":"2021","journal-title":"Food Funct."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1134\/S002689331901014X","article-title":"Possible Involvement of Genes Related to Lysosomal Storage Disorders in the Pathogenesis of Parkinson\u2019s Disease","volume":"53","author":"Rudenok","year":"2019","journal-title":"Mol. Biol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"8090","DOI":"10.1007\/s12035-016-0261-0","article-title":"Decreased Anxiety-Related Behaviour but Apparently Unperturbed NUMB Function in Ligand of NUMB Protein-X (LNX) 1\/2 Double Knockout Mice","volume":"54","author":"Lenihan","year":"2017","journal-title":"Mol. Neurobiol."},{"key":"ref_77","first-page":"123","article-title":"Comparison of Mouse Behavior in the Open Field, Closed and Elevated Cross-Maze Tests by the Use of Factor Analysi","volume":"69","author":"Kovalev","year":"2019","journal-title":"Zhurnal Vyss. Nervn. Deyatelnosti Im. I.P. Pavlov."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"2184","DOI":"10.1093\/bioinformatics\/bts356","article-title":"RSeQC: Quality Control of RNA-Seq Experiments","volume":"28","author":"Wang","year":"2012","journal-title":"Bioinformatics"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"10","DOI":"10.14806\/ej.17.1.200","article-title":"Cutadapt Removes Adapter Sequences from High-Throughput Sequencing Reads","volume":"17","author":"Martin","year":"2011","journal-title":"EMBnet J."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1038\/nmeth.3317","article-title":"HISAT: A Fast Spliced Aligner with Low Memory Requirements","volume":"12","author":"Kim","year":"2015","journal-title":"Nat. Methods"},{"key":"ref_81","unstructured":"Andrews, S. (2023, June 05). FastQC: A Quality Control Tool for High Throughput Sequence Data. Available online: http:\/\/www.bioinformatics.babraham.ac.uk\/projects\/fastqc."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1093\/bioinformatics\/btu638","article-title":"HTSeq\u2014A Python Framework to Work with High-Throughput Sequencing Data","volume":"31","author":"Anders","year":"2015","journal-title":"Bioinformatics"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1186\/s13059-014-0550-8","article-title":"Moderated Estimation of Fold Change and Dispersion for RNA-Seq Data with DESeq2","volume":"15","author":"Love","year":"2014","journal-title":"Genome Biol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.1093\/bioinformatics\/btp101","article-title":"ClueGO: A Cytoscape Plug-in to Decipher Functionally Grouped Gene Ontology and Pathway Annotation Networks","volume":"25","author":"Bindea","year":"2009","journal-title":"Bioinformatics"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1093\/bioinformatics\/btt019","article-title":"CluePedia Cytoscape Plugin: Pathway Insights Using Integrated Experimental and in Silico Data","volume":"29","author":"Bindea","year":"2013","journal-title":"Bioinformatics"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"299","DOI":"10.3171\/JNS\/2008\/108\/2\/0299","article-title":"Increased expression of the glioma-associated antigen ARF4L after loss of the tumor suppressor PTEN. Laboratory investigation","volume":"108","author":"Chi","year":"2008","journal-title":"J. Neurosurg."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1681\/ASN.2009111168","article-title":"mTOR complex-2 activates ENaC by phosphorylating SGK1","volume":"21","author":"Lu","year":"2010","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"9221","DOI":"10.1021\/acsomega.2c07280","article-title":"Role of Autophagy Mediated by AMPK\/DDiT4\/mTOR Axis in HT22 Cells Under Oxygen and Glucose Deprivation\/Reoxygenation","volume":"8","author":"Zhang","year":"2023","journal-title":"ACS Omega"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"17331","DOI":"10.1074\/jbc.M114.631895","article-title":"4E-BPs Control Fat Storage by Regulating the Expression of Egr1 and ATGL","volume":"290","author":"Singh","year":"2015","journal-title":"J. Biol. Chem."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"2658","DOI":"10.1182\/blood-2016-03-703199","article-title":"mTOR signaling: New networks for ALL","volume":"127","author":"Fruman","year":"2016","journal-title":"Blood"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1791","DOI":"10.1080\/15548627.2016.1203483","article-title":"Role for DUSP1 (dual-specificity protein phosphatase 1) in the regulation of autophagy","volume":"12","author":"Wang","year":"2016","journal-title":"Autophagy"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1016\/j.cellsig.2016.04.004","article-title":"Interleukin-6 influences stress-signalling by reducing the expression of the mTOR-inhibitor REDD1 in a STAT3-dependent manner","volume":"28","author":"Pinno","year":"2016","journal-title":"Cell Signal"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"18304","DOI":"10.1074\/jbc.M115.638064","article-title":"Nuclear Receptor Nr4a2 Promotes Alternative Polarization of Macrophages and Confers Protection in Sepsis","volume":"290","author":"Mahajan","year":"2015","journal-title":"J. Biol. Chem."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/15\/12164\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:22:09Z","timestamp":1760127729000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/15\/12164"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,7,29]]},"references-count":93,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2023,8]]}},"alternative-id":["ijms241512164"],"URL":"https:\/\/doi.org\/10.3390\/ijms241512164","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,7,29]]}}}