{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T20:55:53Z","timestamp":1781211353270,"version":"3.54.1"},"reference-count":85,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2021,5,18]],"date-time":"2021-05-18T00:00:00Z","timestamp":1621296000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003407","name":"Ministero dell\u2019Istruzione, dell\u2019Universit\u00e0 e della Ricerca","doi-asserted-by":"publisher","award":["2017M42834"],"award-info":[{"award-number":["2017M42834"]}],"id":[{"id":"10.13039\/501100003407","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Rhes is one of the most interesting genes regulated by thyroid hormones that, through the inhibition of the striatal cAMP\/PKA pathway, acts as a modulator of dopamine neurotransmission. Rhes mRNA is expressed at high levels in the dorsal striatum, with a medial-to-lateral expression gradient reflecting that of both dopamine D2 and adenosine A2A receptors. Rhes transcript is also present in the hippocampus, cerebral cortex, olfactory tubercle and bulb, substantia nigra pars compacta (SNc) and ventral tegmental area of the rodent brain. In line with Rhes-dependent regulation of dopaminergic transmission, data showed that lack of Rhes enhanced cocaine- and amphetamine-induced motor stimulation in mice. Previous studies showed that pharmacological depletion of dopamine significantly reduces Rhes mRNA levels in rodents, non-human primates and Parkinson\u2019s disease (PD) patients, suggesting a link between dopaminergic innervation and physiological Rhes mRNA expression. Rhes protein binds to and activates striatal mTORC1, and modulates L-DOPA-induced dyskinesia in PD rodent models. Finally, Rhes is involved in the survival of mouse midbrain dopaminergic neurons of SNc, thus pointing towards a Rhes-dependent modulation of autophagy and mitophagy processes, and encouraging further investigations about mechanisms underlying dysfunctions of the nigrostriatal system.<\/jats:p>","DOI":"10.3390\/ijms22105326","type":"journal-article","created":{"date-parts":[[2021,5,18]],"date-time":"2021-05-18T23:34:46Z","timestamp":1621380886000},"page":"5326","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Involvement of the Protein Ras Homolog Enriched in the Striatum, Rhes, in Dopaminergic Neurons\u2019 Degeneration: Link to Parkinson\u2019s Disease"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4025-7233","authenticated-orcid":false,"given":"Marcello","family":"Serra","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences, Section of Neuroscience, University of Cagliari, 09042 Cagliari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4911-1735","authenticated-orcid":false,"given":"Annalisa","family":"Pinna","sequence":"additional","affiliation":[{"name":"National Research Council of Italy (CNR), Neuroscience Institute\u2014Cagliari, Cittadella Universitaria, 09042 Cagliari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Costa","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Section of Neuroscience, University of Cagliari, 09042 Cagliari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Usiello","sequence":"additional","affiliation":[{"name":"Department of Environmental, Biological and Pharmaceutical Sciences and Technologies, University of Campania Luigi Vanvitelli, 81100 Caserta, Italy"},{"name":"Laboratory of Behavioral Neuroscience, Ceinge Biotecnologie Avanzate, 80145 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0844-8139","authenticated-orcid":false,"given":"Massimo","family":"Pasqualetti","sequence":"additional","affiliation":[{"name":"Unit of Cell and Developmental Biology, Department of Biology, University of Pisa, 56127 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luigi","family":"Avallone","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine and Animal Productions, University of Naples \u201cFederico II\u201d, 80137 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Micaela","family":"Morelli","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Section of Neuroscience, University of Cagliari, 09042 Cagliari, Italy"},{"name":"National Research Council of Italy (CNR), Neuroscience Institute\u2014Cagliari, Cittadella Universitaria, 09042 Cagliari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0884-1851","authenticated-orcid":false,"given":"Francesco","family":"Napolitano","sequence":"additional","affiliation":[{"name":"Laboratory of Behavioral Neuroscience, Ceinge Biotecnologie Avanzate, 80145 Naples, Italy"},{"name":"Department of Veterinary Medicine and Animal Productions, University of Naples \u201cFederico II\u201d, 80137 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,5,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"4915","DOI":"10.1523\/JNEUROSCI.14-08-04915.1994","article-title":"Isolation of clones of rat striatum-specific mRNAs by directional tag PCR subtraction","volume":"14","author":"Usui","year":"1994","journal-title":"J. Neurosci."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1038\/349117a0","article-title":"The GTPase superfamily: Conserved structure and molecular mechanism","volume":"349","author":"Bourne","year":"1991","journal-title":"Nature"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2014\/308535","article-title":"Small G proteins Dexras1 and RHES and their role in pathophysiological processes","volume":"2014","author":"Thapliyal","year":"2014","journal-title":"Int. J. Cell Biol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1038\/sj.onc.1207161","article-title":"The small GTP-binding protein, Rhes, regulates signal transduction from G protein-coupled receptors","volume":"23","author":"Vargiu","year":"2004","journal-title":"Oncogene"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1159\/000204075","article-title":"The cationic region of Rhes mediates its interactions with specific Gbeta subunits","volume":"23","author":"Hill","year":"2009","journal-title":"Cell Physiol. Biochem."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1007\/s00401-021-02279-2","article-title":"Patterns of neuronal Rhes as a novel hallmark of tauopathies","volume":"141","author":"Ehrenberg","year":"2021","journal-title":"Acta Neuropathol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"782","DOI":"10.1002\/(SICI)1097-4547(19990915)57:6<782::AID-JNR3>3.0.CO;2-9","article-title":"Rhes: A striatal-specific Ras homolog related to Dexras1","volume":"57","author":"Falk","year":"1999","journal-title":"J. Neurosci. Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"eaat3005","DOI":"10.1126\/scitranslmed.aat3005","article-title":"A farnesyltransferase inhibitor activates lysosomes and reduces tau pathology in mice with tauopathy","volume":"11","author":"Hernandez","year":"2019","journal-title":"Sci. Transl. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1016\/j.mcn.2007.10.007","article-title":"The GTP-binding protein Rhes modulates dopamine signalling in striatal medium spiny neurons","volume":"37","author":"Errico","year":"2008","journal-title":"Mol. Cell. Neurosci."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/srep10933","article-title":"Rhes influences striatal cAMP\/PKA-dependent signaling and synaptic plasticity in a gender-sensitive fashion","volume":"5","author":"Ghiglieri","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1016\/j.nbd.2015.03.021","article-title":"Rhes regulates dopamine D2 receptor transmission in striatal cholinergic interneurons","volume":"78","author":"Sciamanna","year":"2015","journal-title":"Neurobiol. Dis."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1016\/j.neuroscience.2005.08.017","article-title":"Rhes, the Ras homolog enriched in striatum, is reduced under conditions of dopamine supersensitivity","volume":"137","author":"Harrison","year":"2006","journal-title":"Neuroscience"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.brainres.2008.09.066","article-title":"Ontogeny and dopaminergic regulation in brain of Ras homolog enriched in striatum (Rhes)","volume":"1245","author":"Harrison","year":"2008","journal-title":"Brain Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1002\/ar.1092310416","article-title":"Heterogeneous distribution of dopamine D2 receptor mRNA in the rat striatum: A quantitative analysis with in situ hybridization histochemistry","volume":"231","author":"Szele","year":"1991","journal-title":"Anat. Rec."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1002\/mds.26489","article-title":"The small GTP-binding protein Rhes influences nigrostriatal-dependent motor behavior during aging","volume":"31","author":"Pinna","year":"2016","journal-title":"Mov. Disord."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"916","DOI":"10.1038\/npp.2015.228","article-title":"Rasd2 modulates prefronto-striatal phenotypes in humans and \u201cSchizophrenia-like behaviors\u201d in mice","volume":"41","author":"Vitucci","year":"2016","journal-title":"Neuropsychopharmacology"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"5480","DOI":"10.1210\/en.2003-0633","article-title":"Differential effects of triiodothyronine and the thyroid hormone receptor beta-specific agonist GC-1 on thyroid hormone target genes in the b ain","volume":"144","author":"Manzano","year":"2003","journal-title":"Endocrinology"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1016\/j.nbd.2008.05.015","article-title":"T3 administration in adult hypothyroid mice modulates expression of proteins involved in striatal synaptic plasticity and improves motor behavior","volume":"31","author":"Vallortigara","year":"2008","journal-title":"Neurobiol. Dis."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0169-328X(01)00140-1","article-title":"Thyroid hormone regulation of rhes, a novel Ras homolog gene expressed in the striatum","volume":"94","author":"Vargiu","year":"2001","journal-title":"Brain Res. Mol. Brain Res."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Napolitano, F., Warren, E.B., Migliarini, S., Punzo, D., Errico, F., Li, Q., Thiolat, M.-L., Vescovi, A.L., Calabresi, P., and Bezard, E. (2017). Decreased Rhes mRNA levels in the brain of patients with Parkinson\u2019s disease and MPTP-treated macaques. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0181677"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"874","DOI":"10.1002\/jnr.22604","article-title":"Rhes and AGS1\/Dexras1 affect signaling by dopamine D1 receptors through adenylyl cyclase","volume":"89","author":"Harrison","year":"2011","journal-title":"J. Neurosci. Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"C1417","DOI":"10.1152\/ajpcell.00341.2008","article-title":"The monomeric G proteins AGS1 and Rhes selectively influence Galphai-dependent signaling to modulate N-type (CaV2.2) calcium channels","volume":"295","author":"Thapliyal","year":"2008","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"ra111","DOI":"10.1126\/scisignal.aaf6670","article-title":"RasGRP1 promotes amphetamine-induced motor behavior through a Rhes interaction network (\u201cRhesactome\u201d) in the striatum","volume":"9","author":"Shahani","year":"2016","journal-title":"Sci. Signal."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"15294","DOI":"10.1038\/s41598-019-51839-w","article-title":"The striatal-enriched protein Rhes is a critical modulator of cocaine-induced molecular and behavioral responses","volume":"9","author":"Napolitano","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1016\/j.neuroscience.2018.05.027","article-title":"The thyroid hormone-target gene Rhes a novel crossroad for neurological and psychiatric disorders: New insights from animal models","volume":"384","author":"Napolitano","year":"2018","journal-title":"Neuroscience"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/j.neulet.2012.05.073","article-title":"Striatum specific protein, Rhes regulates AKT pathway","volume":"521","author":"Bang","year":"2012","journal-title":"Neurosci. Lett."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.neuroscience.2012.12.062","article-title":"Effects of the Ras homolog Rhes on Akt\/protein kinase B and glycogen synthase kinase 3 phosphorylation in striatum","volume":"236","author":"Harrison","year":"2013","journal-title":"Neuroscience"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1016\/j.tips.2007.02.006","article-title":"The Akt-GSK-3 signaling cascade in the actions of dopamine","volume":"28","author":"Beaulieu","year":"2007","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1042\/BJ20100158","article-title":"Mechanisms, regulation and consequences of protein SUMOylation","volume":"428","author":"Wilkinson","year":"2010","journal-title":"Biochem. J."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1007\/978-3-319-50044-7_16","article-title":"Sumoylation: Implications for Neurodegenerative Diseases","volume":"963","author":"Anderson","year":"2017","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1038\/nn.2994","article-title":"Rhes, a striatal-enriched small G protein, mediates mTOR signaling and L-DOPA-induced dyskinesia","volume":"15","author":"Subramaniam","year":"2011","journal-title":"Nat. Neurosci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1327","DOI":"10.1126\/science.1172871","article-title":"Rhes, a striatal specific protein, mediates mutant-huntingtin cytotoxicity","volume":"324","author":"Subramaniam","year":"2009","journal-title":"Science"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1820","DOI":"10.1096\/fj.12-219220","article-title":"A novel human embryonic stem cell-derived Huntington\u2019s disease neuronal model exhibits mutant huntingtin (mHTT) aggregates and soluble mHTT-dependent neurodegeneration","volume":"27","author":"Lu","year":"2013","journal-title":"FASEB J."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"20428","DOI":"10.1074\/jbc.C110.127191","article-title":"Rhes, a physiologic regulator of sumoylation, enhances cross-sumoylation between the basic sumoylation enzymes E1 and Ubc9","volume":"285","author":"Subramaniam","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"4206","DOI":"10.1523\/JNEUROSCI.3730-12.2013","article-title":"Rhes deletion is neuroprotective in the 3-nitropropionic acid model of Huntington\u2019s disease","volume":"33","author":"Mealer","year":"2013","journal-title":"J. Neurosci."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Baiamonte, B.A., Lee, F.A., Brewer, S.T., Spano, D., and LaHoste, G.J. (2013). Attenuation of Rhes activity significantly delays the appearance of behavioral symptoms in a mouse model of Huntington\u2019s disease. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0053606"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.nbd.2015.05.011","article-title":"Ectopic expression of the striatal-enriched GTPase Rhes elicits cerebellar degeneration and an ataxia phenotype in Huntington\u2019s disease","volume":"82","author":"Swarnkar","year":"2015","journal-title":"Neurobiol. Dis."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"20265","DOI":"10.1073\/pnas.2002283117","article-title":"Loss of Hap1 selectively promotes striatal degeneration in Huntington disease mice","volume":"117","author":"Liu","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"890","DOI":"10.1016\/j.celrep.2013.08.001","article-title":"Golgi protein ACBD3 mediates neurotoxicity associated with Huntington\u2019s disease","volume":"4","author":"Sbodio","year":"2013","journal-title":"Cell Rep."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1972","DOI":"10.1083\/jcb.201807068","article-title":"Rhes travels from cell to cell and transports Huntington disease protein via TNT-like protrusion","volume":"218","author":"Sharma","year":"2019","journal-title":"J. Cell. Biol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"13","DOI":"10.3233\/JPD-120155","article-title":"mTOR inhibition alleviates L-DOPA-induced dyskinesia in parkinsonian rats","volume":"3","author":"Decressac","year":"2013","journal-title":"J. Parkinsons Dis."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"ra36","DOI":"10.1126\/scisignal.2000308","article-title":"Inhibition of mTOR signaling in Parkinson\u2019s disease prevents L-DOPA-induced dyskinesia","volume":"2","author":"Santini","year":"2009","journal-title":"Sci. Signal."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1264","DOI":"10.1002\/mds.27115","article-title":"Past, present, and future of Parkinson\u2019s disease: A special essay on the 200th anniversary of the Shaking Palsy","volume":"32","author":"Obeso","year":"2017","journal-title":"Mov. Disord."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1106","DOI":"10.1016\/S1474-4422(10)70218-0","article-title":"Levodopa-induced dyskinesias in patients with Parkinson\u2019s disease: Filling the bench-to-bedside gap","volume":"9","author":"Calabresi","year":"2010","journal-title":"Lancet Neurol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1016\/j.tins.2007.03.005","article-title":"Dopamine dysregulation of movement control in L-DOPA-induced dyskinesia","volume":"30","author":"Cenci","year":"2007","journal-title":"Trends Neurosci."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"S1","DOI":"10.1212\/WNL.0b013e3181a1d44c","article-title":"The scientific and clinical basis for the treatment of Parkinson disease","volume":"72","author":"Olanow","year":"2009","journal-title":"Neurology"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1038\/nn1040","article-title":"Loss of bidirectional striatal synaptic plasticity in L-DOPA-induced dyskinesia","volume":"6","author":"Picconi","year":"2003","journal-title":"Nat. Neurosci."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1038\/nrn2471","article-title":"Molecular mechanisms of L-DOPA-induced dyskinesia","volume":"9","author":"Jenner","year":"2008","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1187","DOI":"10.1016\/j.neuropharm.2010.10.025","article-title":"Huntington\u2019s disease is a disorder of the corpus striatum: Focus on Rhes (Ras homologue enriched in the striatum)","volume":"60","author":"Subramaniam","year":"2011","journal-title":"Neuropharmacology"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/j.nbd.2015.10.020","article-title":"Genetic deletion of Rhes or pharmacological blockade of mTORC1 prevent striato-nigral neurons activation in levodopa-induced dyskinesia","volume":"85","author":"Brugnoli","year":"2016","journal-title":"Neurobiol. Dis."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"eaaz7001","DOI":"10.1126\/sciadv.aaz7001","article-title":"RasGRP1 is a causal factor in the development of l-DOPA-induced dyskinesia in Parkinson\u2019s disease","volume":"6","author":"Eshraghi","year":"2020","journal-title":"Sci. Adv."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1038\/42166","article-title":"Alpha-synuclein in Lewy bodies","volume":"388","author":"Spillantini","year":"1997","journal-title":"Nature"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1120","DOI":"10.1126\/science.1098966","article-title":"Biomedicine. Parkinson\u2019s\u2013Divergent causes, convergent mechanisms","volume":"304","author":"Greenamyre","year":"2004","journal-title":"Science"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1049","DOI":"10.1002\/mds.23732","article-title":"Etiology and pathogenesis of Parkinson\u2019s disease","volume":"26","author":"Schapira","year":"2011","journal-title":"Mov. Disord."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"a008888","DOI":"10.1101\/cshperspect.a008888","article-title":"Genetics of Parkinson\u2019s disease","volume":"2","author":"Klein","year":"2012","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1379","DOI":"10.1095\/biolreprod.102.003848","article-title":"Protective effects of estrogen and selective estrogen receptor modulators in the brain","volume":"67","author":"Dhandapani","year":"2002","journal-title":"Biol. Reprod."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1016\/j.yfrne.2014.02.002","article-title":"Sex differences in Parkinson\u2019s disease","volume":"35","author":"Gillies","year":"2014","journal-title":"Front. Neuroendocrinol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1126\/science.abb8587","article-title":"Microglia modulate neurodegeneration in Alzheimer\u2019s and Parkinson\u2019s diseases","volume":"370","author":"Bartels","year":"2020","journal-title":"Science"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1092","DOI":"10.1097\/NEN.0b013e3181b767b4","article-title":"Kinetics of microglial activation and degeneration of dopamine-containing neurons in a rat model of Parkinson disease induced by 6-hydroxydopamine","volume":"68","author":"Henry","year":"2009","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1763","DOI":"10.1523\/JNEUROSCI.22-05-01763.2002","article-title":"Blockade of microglial activation is neuroprotective in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model of Parkinson disease","volume":"22","author":"Wu","year":"2002","journal-title":"J. Neurosci."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"163","DOI":"10.3389\/fnagi.2018.00163","article-title":"Rhes counteracts dopamine neuron degeneration and neuroinflammation depending on gender and age","volume":"10","author":"Costa","year":"2018","journal-title":"Front. Aging Neurosci."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1002\/hup.766","article-title":"Patterns of simultaneous polysubstance use in drug using university students","volume":"21","author":"Barrett","year":"2006","journal-title":"Hum. Psychopharmacol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"802","DOI":"10.4103\/1673-5374.268895","article-title":"Neuronal and peripheral damages induced by synthetic psychoactive substances: An update of recent findings from human and animal studies","volume":"15","author":"Simola","year":"2020","journal-title":"Neural Regen. Res."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/S1054-139X(01)00315-9","article-title":"Increasing MDMA use among college students: Results of a national survey","volume":"30","author":"Strote","year":"2002","journal-title":"J. Adolesc. Health"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1007\/s00213-006-0322-6","article-title":"3,4-Methylenedioxymethamphetamine (MDMA) neurotoxicity in rats: A reappraisal of past and present findings","volume":"189","author":"Baumann","year":"2007","journal-title":"Psychopharmacology"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1177\/0269881106061153","article-title":"Ecstasy: Are animal data consistent between species and can they translate to humans?","volume":"20","author":"Easton","year":"2006","journal-title":"J. Psychopharmacol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1016\/j.pbb.2007.10.003","article-title":"Actions of 3,4-methylenedioxymethamphetamine (MDMA) on cerebral dopaminergic, serotonergic and cholinergic neurons","volume":"90","author":"Gudelsky","year":"2008","journal-title":"Pharmacol. Biochem. Behav."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1002\/hup.351","article-title":"Human psychopharmacology of Ecstasy (MDMA): A review of 15 years of empirical research","volume":"16","author":"Parrott","year":"2001","journal-title":"Hum. Psychopharmacol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1007\/s12640-017-9761-6","article-title":"Progression and persistence of neurotoxicity induced by MDMA in dopaminergic regions of the mouse brain and association with noradrenergic, GABAergic, and serotonergic damage","volume":"32","author":"Costa","year":"2017","journal-title":"Neurotox. Res."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/j.neuro.2016.07.008","article-title":"Effect of crowding, temperature and age on glia activation and dopaminergic neurotoxicity induced by MDMA in the mouse brain","volume":"56","author":"Frau","year":"2016","journal-title":"Neurotoxicology"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1102","DOI":"10.1111\/j.1471-4159.2008.05705.x","article-title":"Persistent MDMA-induced dopaminergic neurotoxicity in the striatum and substantia nigra of mice","volume":"107","author":"Granado","year":"2008","journal-title":"J. Neurochem."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/j.pneurobio.2015.09.011","article-title":"Amphetamine-related drugs neurotoxicity in humans and in experimental animals: Main mechanisms","volume":"155","author":"Moratalla","year":"2017","journal-title":"Prog. Neurobiol."},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Costa, G., Porceddu, P.F., Serra, M., Casu, M.A., Schiano, V., Napolitano, F., Pinna, A., Usiello, A., and Morelli, M. (2019). Lack of Rhes increases MDMA-induced neuroinflammation and dopamine neuron degeneration: Role of gender and age. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20071556"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"790","DOI":"10.3389\/fendo.2018.00790","article-title":"Hallmarks of aging: An autophagic perspective","volume":"9","author":"Barbosa","year":"2018","journal-title":"Front. Endocrinol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1837","DOI":"10.4161\/cc.6.15.4511","article-title":"Autophagy and human disease","volume":"6","author":"Huang","year":"2007","journal-title":"Cell Cycle"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1038\/cr.2013.168","article-title":"The machinery of macroautophagy","volume":"24","author":"Feng","year":"2014","journal-title":"Cell Res."},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Giorgi, C., Bouhamida, E., Danese, A., Previati, M., Pinton, P., and Patergnani, S. (2021). Relevance of autophagy and mitophagy dynamics and markers in neurodegenerative diseases. Biomedicines, 9.","DOI":"10.3390\/biomedicines9020149"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"682","DOI":"10.1016\/j.cell.2011.07.030","article-title":"Autophagy and aging","volume":"146","author":"Rubinsztein","year":"2011","journal-title":"Cell"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1002\/mds.25462","article-title":"Lysosomal impairment in Parkinson\u2019s disease","volume":"28","author":"Dehay","year":"2013","journal-title":"Mov. Disord."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1038\/s41582-019-0244-7","article-title":"Ageing as a risk factor for neurodegenerative disease","volume":"15","author":"Hou","year":"2019","journal-title":"Nat. Rev. Neurol."},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Lin, K.-J., Chen, S.-D., Liou, C.-W., Chuang, Y.-C., Lin, H.-Y., and Lin, T.-K. (2019). The overcrowded crossroads: Mitochondria, alpha-synuclein, and the endo-lysosomal system interaction in Parkinson\u2019s disease. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20215312"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1038\/s41580-018-0003-4","article-title":"Mechanism and medical implications of mammalian autophagy","volume":"19","author":"Dikic","year":"2018","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"100","DOI":"10.3389\/fnagi.2020.00100","article-title":"Mitochondrial homeostasis and signaling in Parkinson\u2019s disease","volume":"12","author":"Scorziello","year":"2020","journal-title":"Front. Aging Neurosci."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"e1900231","DOI":"10.1002\/bies.201900231","article-title":"Rhes tunnels: A radical new way of communication in the brain\u2019s striatum?","volume":"42","author":"Subramaniam","year":"2020","journal-title":"Bioessays"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"3547","DOI":"10.1074\/jbc.M113.536912","article-title":"Rhes, a striatal-selective protein implicated in Huntington disease, binds beclin-1 and activates autophagy","volume":"289","author":"Mealer","year":"2014","journal-title":"J. Biol. Chem."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/10\/5326\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:03:41Z","timestamp":1760162621000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/10\/5326"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,5,18]]},"references-count":85,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2021,5]]}},"alternative-id":["ijms22105326"],"URL":"https:\/\/doi.org\/10.3390\/ijms22105326","relation":{"has-preprint":[{"id-type":"doi","id":"10.20944\/preprints202104.0379.v1","asserted-by":"object"}]},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,5,18]]}}}