{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T15:48:05Z","timestamp":1790696885959,"version":"4.1.0"},"reference-count":291,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2023,3,21]],"date-time":"2023-03-21T00:00:00Z","timestamp":1679356800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Lugli Donation"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Alpha-Synuclein (\u03b1-Syn) is one of the most important molecules involved in the pathogenesis of Parkinson\u2019s disease and related disorders, synucleinopathies, but also in several other neurodegenerative disorders with a more elusive role. This review analyzes the activities of \u03b1-Syn, in different conformational states, monomeric, oligomeric and fibrils, in relation to neuronal dysfunction. The neuronal damage induced by \u03b1-Syn in various conformers will be analyzed in relation to its capacity to spread the intracellular aggregation seeds with a prion-like mechanism. In view of the prominent role of inflammation in virtually all neurodegenerative disorders, the activity of \u03b1-Syn will also be illustrated considering its influence on glial reactivity. We and others have described the interaction between general inflammation and cerebral dysfunctional activity of \u03b1-Syn. Differences in microglia and astrocyte activation have also been observed when in vivo the presence of \u03b1-Syn oligomers has been combined with a lasting peripheral inflammatory effect. The reactivity of microglia was amplified, while astrocytes were damaged by the double stimulus, opening new perspectives for the control of inflammation in synucleinopathies. Starting from our studies in experimental models, we extended the perspective to find useful pointers to orient future research and potential therapeutic strategies in neurodegenerative disorders.<\/jats:p>","DOI":"10.3390\/ijms24065914","type":"journal-article","created":{"date-parts":[[2023,3,21]],"date-time":"2023-03-21T03:15:03Z","timestamp":1679368503000},"page":"5914","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":110,"title":["Alpha Synuclein: Neurodegeneration and Inflammation"],"prefix":"10.3390","volume":"24","author":[{"given":"Gianluigi","family":"Forloni","sequence":"first","affiliation":[{"name":"Department of Neuroscience, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Via Mario Negri 2, 20156 Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/S0197-4580(02)00065-9","article-title":"Staging of brain pathology related to sporadic Parkinson\u2019s disease","volume":"24","author":"Braak","year":"2003","journal-title":"Neurobiol. Aging"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"De Nuccio, F., Kashyrina, M., Serinelli, F., Laferri\u00e8re, F., Lofrumento, D.D., De Giorgi, F., and Ichas, F. (2023). Oligodendrocytes Prune Axons Containing \u03b1-Synuclein Aggregates In Vivo: Lewy Neurites as Precursors of Glial Cytoplasmic Inclusions in Multiple System Atrophy?. Biomolecules, 13.","DOI":"10.3390\/biom13020269"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1136\/jnnp.52.1.67","article-title":"Anti-ubiquitin immunocytochemistry is more sensitive than conventional techniques in the detection of diffuse Lewy body disease","volume":"52","author":"Lennox","year":"1989","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1038\/ng0298-106","article-title":"Ala30Pro mutation in the gene encoding alpha-synuclein in Parkinson\u2019s disease","volume":"18","author":"Kuhn","year":"1998","journal-title":"Nat. Genet."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2045","DOI":"10.1126\/science.276.5321.2045","article-title":"Mutation in the alpha-synuclein gene identified in families with Parkinson\u2019s disease","volume":"276","author":"Polymeropoulos","year":"1997","journal-title":"Science"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"11282","DOI":"10.1073\/pnas.90.23.11282","article-title":"Molecular cloning of cDNA encoding an unrecognized component of amyloid in Alzheimer disease","volume":"90","author":"Ueda","year":"1993","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"9141","DOI":"10.1073\/pnas.92.20.9141","article-title":"NACP, the precursor protein of the non-amyloid beta\/A4 protein (A beta) component of Alzheimer disease amyloid, binds A beta and stimulates A beta aggregation","volume":"92","author":"Yoshimoto","year":"1995","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1038\/42166","article-title":"\u03b1-Synuclein in Lewy bodies","volume":"388","author":"Spillantini","year":"1997","journal-title":"Nature"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"6469","DOI":"10.1073\/pnas.95.11.6469","article-title":"\u03b1-Synuclein in filamentous inclusions of Lewy bodies from Parkinson\u2019s disease and dementia with lewy bodies","volume":"95","author":"Spillantini","year":"1998","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"3204","DOI":"10.1093\/brain\/awx275","article-title":"Synaptic phosphorylated \u03b1-synuclein in dementia with Lewy bodies","volume":"140","author":"Pegueroles","year":"2017","journal-title":"Brain"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1038\/ncb748","article-title":"alpha-Synuclein is phosphorylated in synucleinopathy lesions","volume":"4","author":"Fujiwara","year":"2002","journal-title":"Nat. Cell Biol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1713","DOI":"10.1096\/fj.04-1621fje","article-title":"Protective effect of TAT-delivered alpha-synuclein: Relevance of the C-terminal domain and involvement of HSP70","volume":"18","author":"Albani","year":"2004","journal-title":"FASEB J."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1038\/nature10324","article-title":"\u03b1-Synuclein Occurs Physiologically as a Helically Folded Tetramer that Resists Aggregation","volume":"477","author":"Bartels","year":"2011","journal-title":"Nature"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"17797","DOI":"10.1073\/pnas.1113260108","article-title":"A Soluble \u03b1-Synuclein Construct Forms a Dynamic Tetramer","volume":"108","author":"Wang","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"12036","DOI":"10.1039\/C9CP02464F","article-title":"On the ubiquity of helical \u03b1-synuclein tetramers","volume":"21","author":"Xu","year":"2019","journal-title":"Phys. Chem. Chem. Phys."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"9596","DOI":"10.1073\/pnas.1505953112","article-title":"KTKEGV repeat motifs are key mediators of normal \u03b1-synuclein tetramerization: Their mutation causes excess monomers and neurotoxicity","volume":"112","author":"Dettmer","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"822420","DOI":"10.3389\/fnins.2022.822420","article-title":"Oligomeropathies, inflammation and prion protein binding","volume":"16","author":"Forloni","year":"2022","journal-title":"Front. Neurosci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"E4","DOI":"10.1038\/nature12125","article-title":"Properties of Native Brain \u03b1-Synuclein","volume":"498","author":"Vivona","year":"2013","journal-title":"Nature"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"7314","DOI":"10.1038\/ncomms8314","article-title":"Parkinson-Causing \u03b1-Synuclein Missense Mutations Shift Native Tetramers to Monomers as a Mechanism for Disease Initiation","volume":"6","author":"Dettmer","year":"2015","journal-title":"Nat. Commun."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1038\/s41531-022-00380-1","article-title":"Parkinson-causing mutations in LRRK2 impair the physiological tetramerization of endogenous \u03b1-synuclein in human neurons","volume":"8","author":"Stricker","year":"2022","journal-title":"NP J. Parkinsons. Dis."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"167714","DOI":"10.1016\/j.jmb.2022.167714","article-title":"Functional and Pathological Effects of \u03b1-Synuclein on Synaptic SNARE Complexes","volume":"435","author":"Gao","year":"2023","journal-title":"J. Mol. Biol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/j.tins.2022.11.007","article-title":"\u03b1-Synuclein in synaptic function and dysfunction","volume":"46","author":"Sharma","year":"2023","journal-title":"Trends Neurosci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"6810","DOI":"10.1038\/s41467-022-34552-7","article-title":"The 3D structure of lipidic fibrils of \u03b1-synuclein","volume":"13","author":"Frieg","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"3827","DOI":"10.1038\/ncomms4827","article-title":"Direct Observation of the Three Regions in \u03b1-Synuclein That Determine Its Membrane-Bound Behaviour","volume":"5","author":"Fusco","year":"2014","journal-title":"Nat. Commun."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1440","DOI":"10.1126\/science.aan6160","article-title":"Structural basis of membrane disruption and cellular toxicity by \u03b1-synuclein oligomers","volume":"358","author":"Fusco","year":"2017","journal-title":"Science"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/S0304-3940(00)01153-8","article-title":"Full length alpha-synuclein is present in cerebrospinal fluid from Parkinson\u2019s disease and normal subjects","volume":"287","author":"Borghi","year":"2000","journal-title":"Neurosci. Lett."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1038\/nm1747","article-title":"Lewy body-like pathology in long-term embryonic nigral transplants in Parkinson\u2019s disease","volume":"14","author":"Kordower","year":"2008","journal-title":"Nat. Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1038\/nm1746","article-title":"Lewy bodies in grafted neurons in subjects with Parkinson\u2019s disease suggest host-to-graft disease propagation","volume":"14","author":"Li","year":"2008","journal-title":"Nat. Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1038\/nature09768","article-title":"Prion propagation and toxicity in vivo occur in two distinct mechanistic phases","volume":"470","author":"Sandberg","year":"2011","journal-title":"Nature"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1002\/mds.26624","article-title":"Oligomeropathies and pathogenesis of Alzheimer and Parkinson\u2019s diseases","volume":"31","author":"Forloni","year":"2016","journal-title":"Mov. Disord."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1016\/j.bbi.2018.02.012","article-title":"Alpha-synuclein oligomers impair memory through glial cell activation and via Toll-like receptor 2","volume":"69","author":"Balducci","year":"2018","journal-title":"Brain Behav. Immun."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1386","DOI":"10.1038\/s41467-020-15119-w","article-title":"Microglia clear neuron-released \u03b1-synuclein via selective autophagy and prevent neurodegeneration","volume":"11","author":"Choi","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"6386","DOI":"10.1007\/s00415-022-11258-w","article-title":"Dysregulation of peripheral monocytes and pro-inflammation of alpha-synuclein in Parkinson\u2019s disease","volume":"269","author":"Su","year":"2022","journal-title":"J. Neurol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1186\/s13024-017-0195-7","article-title":"Toll-like receptor 4 stimulation with monophosphoryl lipid A ameliorates motor deficits and nigral neurodegeneration triggered by extraneuronal \u03b1-synucleinopathy","volume":"12","author":"Venezia","year":"2017","journal-title":"Mol. Neurodegener."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1016\/j.bbi.2020.01.018","article-title":"Peripheral innate immune and bacterial signals relate to clinical heterogeneity in Parkinson\u2019s disease","volume":"87","author":"Wijeyekoon","year":"2020","journal-title":"Brain Behav. Immun."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1111\/nan.12644","article-title":"Peripheral inflammation exacerbates \u03b1-synuclein toxicity and neuropathology in Parkinson\u2019s models","volume":"47","author":"Balducci","year":"2021","journal-title":"Neuropathol. Appl. Neurobiol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1055","DOI":"10.1016\/0092-8674(93)90635-4","article-title":"Seeding \u201cone-dimensional crystallization\u201d of amyloid: A pathogenic mechanism in Alzheimer\u2019s disease and scrapie?","volume":"73","author":"Jarrett","year":"1993","journal-title":"Cell"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Giamp\u00e0, M., Amundarain, M.J., Herrera, M.G., Tonali, N., and Dodero, V.I. (2021). Implementing Complementary Approaches to Shape the Mechanism of \u03b1-Synuclein Oligomerization as a Model of Amyloid Aggregation. Molecules, 27.","DOI":"10.3390\/molecules27010088"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1044","DOI":"10.1038\/s41594-019-0322-y","article-title":"Structures of fibrils formed by \u03b1-synuclein hereditary disease mutant H50Q reveal new polymorphs","volume":"26","author":"Boyer","year":"2019","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"e36402","DOI":"10.7554\/eLife.36402","article-title":"Cryo-EM structure of alpha-synuclein fibrils","volume":"7","author":"Taylor","year":"2018","journal-title":"Elife"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1038\/s41422-020-0299-4","article-title":"Cryo-EM structure of full-length \u03b1-synuclein amyloid fibril with Parkinson\u2019s disease familial A53T mutation","volume":"30","author":"Sun","year":"2020","journal-title":"Cell Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2643","DOI":"10.1038\/s41467-020-16386-3","article-title":"Parkinson\u2019s disease associated mutation E46K of \u03b1-synuclein triggers the formation of a distinct fibril structure","volume":"11","author":"Zhao","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1186\/s13024-021-00501-z","article-title":"Neuropathology and molecular diagnosis of Synucleinopathies","volume":"16","author":"Koga","year":"2021","journal-title":"Mol. Neurodegener."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1038\/s41586-022-05319-3","article-title":"Structures of \u03b1-synuclein filaments from human brains with Lewy pathology","volume":"610","author":"Yang","year":"2022","journal-title":"Nature"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"999","DOI":"10.1002\/2211-5463.13110","article-title":"Seeded assembly in vitro does not replicate the structures of \u03b1-synuclein filaments from multiple system atrophy","volume":"11","author":"Schweighauser","year":"2021","journal-title":"FEBS Open Bio"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"105966","DOI":"10.1016\/j.nbd.2022.105966","article-title":"Monitoring \u03b1-synuclein aggregation","volume":"176","author":"Arotcarena","year":"2023","journal-title":"Neurobiol. Dis."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"878869","DOI":"10.3389\/fnins.2022.878869","article-title":"General Principles Underpinning Amyloid Structure","volume":"16","author":"Taylor","year":"2022","journal-title":"Front. Neurosci."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"e43584","DOI":"10.7554\/eLife.43584","article-title":"Heparin-induced tau filaments are polymorphic and differ from those in Alzheimer\u2019s and Pick\u2019s diseases","volume":"8","author":"Zhang","year":"2019","journal-title":"Elife"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1042\/bst0300559","article-title":"Aggregation and neurotoxicity of alpha-synuclein and related peptides","volume":"30","author":"Irvine","year":"2002","journal-title":"Biochem. Soc. Trans."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1111\/jnc.14808","article-title":"\u03b1-Synuclein oligomers and fibrils: A spectrum of species, a spectrum of toxicities","volume":"150","author":"Alam","year":"2019","journal-title":"J. Neurochem."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1318","DOI":"10.1038\/3311","article-title":"Accelerated in vitro fibril formation by a mutant alpha-synuclein linked to early-onset Parkinson disease","volume":"4","author":"Conway","year":"1998","journal-title":"Nat. Med."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1073\/pnas.97.2.571","article-title":"Acceleration of oligomerization, not fibrillization, is a shared property of both alpha-synuclein mutations linked to early-onset Parkinson\u2019s disease: Implications for pathogenesis and therapy","volume":"97","author":"Conway","year":"2000","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1089","DOI":"10.1016\/S0022-2836(02)00735-0","article-title":"Alpha-synuclein, especially the Parkinson\u2019s disease-associated mutants, forms pore-like annular and tubular protofibrils","volume":"322","author":"Lashuel","year":"2002","journal-title":"J. Mol. Biol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1038\/418291a","article-title":"Neurodegenerative disease: Amyloid pores from pathogenic mutations","volume":"418","author":"Lashuel","year":"2002","journal-title":"Nature"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/bs.ircmb.2016.08.010","article-title":"Structural Characteristics of \u03b1-Synuclein Oligomers","volume":"329","author":"Cremades","year":"2017","journal-title":"Int. Rev. Cell Mol. Biol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"e2109617119","DOI":"10.1073\/pnas.2109617119","article-title":"\u03b1-Synuclein phosphorylation at serine 129 occurs after initial protein deposition and inhibits seeded fibril formation and toxicity","volume":"119","author":"Ghanem","year":"2022","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1003997","DOI":"10.3389\/fnins.2022.1003997","article-title":"How important is the N-terminal acetylation of alpha-synuclein for its function and aggregation into amyloids?","volume":"16","author":"Lyer","year":"2022","journal-title":"Front. Neurosci."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"323","DOI":"10.5483\/BMBRep.2022.55.7.073","article-title":"Role of post-translational modifications on the alpha-synuclein aggregation-related pathogenesis of Parkinson\u2019s disease","volume":"55","author":"Yoo","year":"2022","journal-title":"BMB Rep."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"3630","DOI":"10.1021\/acs.biochem.9b00629","article-title":"N-Terminal Acetylation Affects \u03b1-Synuclein Fibril Polymorphism","volume":"58","author":"Watson","year":"2019","journal-title":"Biochemistry"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1016\/j.jmb.2019.08.021","article-title":"N-Terminal Ubiquitination of Amyloidogenic Proteins Triggers Removal of Their Oligomers by the Proteasome Holoenzyme","volume":"432","author":"Ye","year":"2020","journal-title":"J. Mol. Biol."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Chen, L., Wei, Y., Wang, X., and He, R. (2010). Ribosylation rapidly induces alpha-synuclein to form highly cytotoxic molten globules of advanced glycation end products. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0009052"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1399","DOI":"10.1093\/brain\/awx056","article-title":"Glycation potentiates \u03b1-synuclein-associated neurodegeneration in synucleinopathies","volume":"140","author":"Szego","year":"2017","journal-title":"Brain"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"167","DOI":"10.3389\/fnagi.2020.00167","article-title":"SUMOylation in \u03b1-Synuclein Homeostasis and Pathology","volume":"12","author":"Savyon","year":"2020","journal-title":"Front. Aging Neurosci."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1048","DOI":"10.1016\/j.cell.2012.03.037","article-title":"Direct observation of the interconversion of normal and toxic forms of \u03b1-synuclein","volume":"149","author":"Cremades","year":"2012","journal-title":"Cell"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1038\/s42003-019-0598-9","article-title":"Alpha-synuclein stepwise aggregation reveals features of an early onset mutation in Parkinson\u2019s disease","volume":"2","author":"Silva","year":"2019","journal-title":"Commun. Biol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1814","DOI":"10.1038\/s41467-021-21937-3","article-title":"The release of toxic oligomers from \u03b1-synuclein fibrils induces dysfunction in neuronal cells","volume":"12","author":"Cascella","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"17482","DOI":"10.1021\/ja9077599","article-title":"Structural properties of pore-forming oligomers of \u03b1-synuclein","volume":"131","author":"Kim","year":"2009","journal-title":"JACS"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1134","DOI":"10.1038\/s41593-022-01140-3","article-title":"Pathological structural conversion of \u03b1-synuclein at the mitochondria induces neuronal toxicity","volume":"25","author":"Choi","year":"2022","journal-title":"Nat. Neurosci."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"2838","DOI":"10.1111\/febs.12824","article-title":"\u03b1-Synuclein oligomers distinctively permeabilize complex model membranes","volume":"281","author":"Stefanovic","year":"2014","journal-title":"FEBS J."},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Caruana, M., Camilleri, A., Farrugia, M.Y., Ghio, S., Jakub\u00ed\u010dkov\u00e1, M., Cauchi, R.J., and Vassallo, N. (2021). Extract from the Marine Seaweed Padina pavonica Protects Mitochondrial Biomembranes from Damage by Amyloidogenic Peptides. Molecules, 26.","DOI":"10.3390\/molecules26051444"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1038\/s41419-019-2091-2","article-title":"Mitochondrial damage by \u03b1-synuclein causes cell death in human dopaminergic neurons","volume":"10","author":"Ganjam","year":"2019","journal-title":"Cell Death Dis."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1007\/s00401-019-01961-w","article-title":"Wide distribution of alpha-synuclein oligomers in multiple system atrophy brain detected by proximity ligation","volume":"137","author":"Sekiya","year":"2019","journal-title":"Acta Neuropathol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1186\/s40478-022-01440-6","article-title":"Discrepancy between distribution of alpha-synuclein oligomers and Lewy-related pathology in Parkinson\u2019s disease","volume":"10","author":"Sekiya","year":"2022","journal-title":"Acta Neuropathol. Commun."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1093\/brain\/awy318","article-title":"Cellular prion protein neither binds to alpha-synuclein oligomers nor mediates their detrimental effects","volume":"142","author":"Beeg","year":"2019","journal-title":"Brain"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"5512","DOI":"10.1038\/s41467-022-33252-6","article-title":"Small soluble \u03b1-synuclein aggregates are the toxic species in Parkinson\u2019s disease","volume":"13","author":"Emin","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_76","first-page":"1513","article-title":"\u03b1-Synuclein in the olfactory system in Parkinson\u2019s disease: Role of neural connections on spreading pathology","volume":"219","year":"2014","journal-title":"Brain Struct. Funct."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1007\/s00441-017-2733-6","article-title":"Propagation of alpha-synuclein pathology from the olfactory bulb: Possible role in the pathogenesis of dementia with Lewy bodies","volume":"373","author":"Cersosimo","year":"2018","journal-title":"Cell Tissue Res."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"879","DOI":"10.1111\/j.1460-9568.2009.06641.x","article-title":"Changes in adult olfactory bulb neurogenesis in mice expressing the A30P mutant form of alpha-synuclein","volume":"29","author":"Marxreiter","year":"2009","journal-title":"Eur. J. Neurosci."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1093\/brain\/awz380","article-title":"\u03b1-Synuclein BAC transgenic mice exhibit RBD-like behaviour and hyposmia: A prodromal Parkinson\u2019s disease model","volume":"43","author":"Taguchi","year":"2020","journal-title":"Brain"},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Zhang, S., Xiao, Q., and Le, W. (2015). Olfactory dysfunction and neurotransmitter disturbance in olfactory bulb of transgenic mice expressing human A53T mutant \u03b1-synuclein. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0119928"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"2036","DOI":"10.1002\/mds.28512","article-title":"\u03b1-Synuclein Spread from Olfactory Bulb Causes Hyposmia, Anxiety, and Memory Loss in BAC-SNCA Mice","volume":"36","author":"Uemura","year":"2021","journal-title":"Mov. Disord."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1759","DOI":"10.1084\/jem.20160368","article-title":"Widespread transneuronal propagation of \u03b1-synucleinopathy triggered in olfactory bulb mimics prodromal Parkinson\u2019s disease","volume":"213","author":"Rey","year":"2016","journal-title":"J. Exp. Med."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1007\/s00401-017-1792-9","article-title":"Spread of aggregates after olfactory bulb injection of \u03b1-synuclein fibrils is associated with early neuronal loss and is reduced long term","volume":"135","author":"Rey","year":"2018","journal-title":"Acta Neuropathol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"2033","DOI":"10.1002\/mds.29161","article-title":"Lewy Body Disease Primate Model with \u03b1-Synuclein Propagation from the Olfactory Bulb","volume":"37","author":"Sawamura","year":"2022","journal-title":"Mov. Disord."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1111\/j.1471-4159.2009.06324.x","article-title":"Seeding induced by alpha-synuclein oligomers provides evidence for spreading of alpha-synuclein pathology","volume":"111","author":"Danzer","year":"2009","journal-title":"J. Neurochem."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1186\/1750-1326-7-42","article-title":"Exosomal cell-to-cell transmission of alpha synuclein oligomers","volume":"7","author":"Danzer","year":"2012","journal-title":"Mol. Neurodegener."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"9220","DOI":"10.1523\/JNEUROSCI.2617-07.2007","article-title":"Different species of alpha-synuclein oligomers induce calcium influx and seeding","volume":"27","author":"Danzer","year":"2007","journal-title":"J. Neurosci."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1074\/jbc.M107045200","article-title":"Membrane-bound-synuclein has a high aggregation propensity and the ability to seed the aggregation of the cytosolic form","volume":"277","author":"Lee","year":"2002","journal-title":"J. Biol. Chem"},{"key":"ref_89","doi-asserted-by":"crossref","unstructured":"Auli\u0107, S., Le, T.T., Moda, F., Abounit, S., Corvaglia, S., Casalis, L., Gustincich, S., Zurzolo, C., Tagliavini, F., and Legname, G. (2014). Defined \u03b1-synuclein prion-like molecular assemblies spreading in cell culture. BMC Neurosci., 15.","DOI":"10.1186\/1471-2202-15-69"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"20051","DOI":"10.1073\/pnas.0908005106","article-title":"Exogenous alpha-synuclein fibrils seed the formation of Lewy body-like intracellular inclusions in cultured cells","volume":"106","author":"Luk","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"6838","DOI":"10.1523\/JNEUROSCI.5699-09.2010","article-title":"Cell-produced alpha-synuclein is secreted in a calcium-dependent manner by exosomes and impacts neuronal survival","volume":"30","author":"Emmanouilidou","year":"2010","journal-title":"J. Neurosci."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"172","DOI":"10.3389\/fnins.2017.00172","article-title":"Investigation of Endocytic Pathways for the Internalization of Exosome-Associated Oligomeric Alpha-Synuclein","volume":"11","author":"Delenclos","year":"2017","journal-title":"Front. Neurosci."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1016\/j.bpj.2020.12.031","article-title":"Internalization of \u03b1-synuclein oligomers into SH-SY5Y cells","volume":"120","author":"Shearer","year":"2021","journal-title":"Biophys. J."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.neurobiolaging.2017.09.016","article-title":"Intercellular transfer of pathogenic \u03b1-synuclein by extracellular vesicles is induced by the lipid peroxidation product 4-hydroxynonenal","volume":"61","author":"Zhang","year":"2018","journal-title":"Neurobiol. Aging."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"1539","DOI":"10.1007\/s10571-018-0622-5","article-title":"Secretion and Uptake of \u03b1-Synuclein Via Extracellular Vesicles in Cultured Cells","volume":"38","author":"Gustafsson","year":"2018","journal-title":"Cell Mol. Neurobiol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/j.neuroscience.2021.06.033","article-title":"Investigation of \u03b1-Synuclein Species in Plasma Exosomes and the Oligomeric and Phosphorylated \u03b1-Synuclein as Potential Peripheral Biomarker of Parkinson\u2019s Disease","volume":"469","author":"Zheng","year":"2021","journal-title":"Neuroscience"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"2135","DOI":"10.1038\/nprot.2014.143","article-title":"Addition of exogenous \u03b1-synuclein preformed fibrils to primary neuronal cultures to seed recruitment of endogenous \u03b1-synuclein to Lewy body and Lewy neurite-like aggregates","volume":"9","author":"Luk","year":"2014","journal-title":"Nat. Protoc."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"5080","DOI":"10.1523\/JNEUROSCI.0060-19.2019","article-title":"\u03b1-Synuclein (\u03b1Syn) Preformed Fibrils Induce Endogenous \u03b1-Syn Aggregation, Compromise Synaptic Activity and Enhance Synapse Loss in Cultured Excitatory Hippocampal Neurons","volume":"39","author":"Wu","year":"2019","journal-title":"J. Neurosci."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1007\/s00401-020-02227-6","article-title":"Neuronal activity modulates alpha-synuclein aggregation and spreading in organotypic brain slice cultures and in vivo","volume":"140","author":"Wu","year":"2020","journal-title":"Acta Neuropathol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/S0014-5793(98)01418-5","article-title":"Aggregates from mutant and wild-type alpha-synuclein proteins and NAC peptide induce apoptotic cell death in human neuroblastoma cells by formation of beta-sheet and amyloid-like filaments","volume":"440","author":"Jakes","year":"1998","journal-title":"FEBS Lett."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"1894","DOI":"10.1007\/PL00000671","article-title":"Alpha-synuclein and Parkinson\u2019s disease","volume":"57","author":"Brice","year":"2000","journal-title":"Cell Mol. Life Sci."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"632","DOI":"10.1002\/1531-8249(200005)47:5<632::AID-ANA11>3.0.CO;2-N","article-title":"Alpha-synuclein and Parkinson\u2019s disease: Selective neurodegenerative effect of alpha-synuclein fragment on dopaminergic neurons in vitro and in vivo","volume":"47","author":"Forloni","year":"2000","journal-title":"Ann. Neurol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1002\/iub.316","article-title":"Oligomeric alpha-synuclein and its role in neuronal death","volume":"62","author":"Brown","year":"2010","journal-title":"IUBMB Life"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1042\/BJ20111924","article-title":"Toxic prefibrillar \u03b1-synuclein amyloid oligomers adopt a distinctive antiparallel \u03b2-sheet structure","volume":"443","author":"Celej","year":"2012","journal-title":"Biochem. J."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"15970","DOI":"10.1021\/ja405993r","article-title":"Membrane remodeling by \u03b1-synuclein and effects on amyloid formation","volume":"135","author":"Jiang","year":"2013","journal-title":"J. Am. Chem. Soc."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"1496","DOI":"10.1093\/brain\/awu057","article-title":"Accumulation of oligomer-prone \u03b1-synuclein exacerbates synaptic and neuronal degeneration in vivo","volume":"137","author":"Rockenstein","year":"2014","journal-title":"Brain"},{"key":"ref_107","doi-asserted-by":"crossref","unstructured":"Bigi, A., Ermini, E., Chen, S.W., Cascella, R., and Cecchi, C. (2021). Exploring the Release of Toxic Oligomers from \u03b1-Synuclein Fibrils with Antibodies and STED Microscopy. Life, 11.","DOI":"10.3390\/life11050431"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"7813","DOI":"10.1073\/pnas.1713129115","article-title":"\u03b1-Synuclein oligomers induce early axonal dysfunction in human iPSC-based models of synucleinopathies","volume":"115","author":"Prots","year":"2018","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"6880","DOI":"10.1038\/s41467-022-34555-4","article-title":"DOPAnization of tyrosine in \u03b1-synuclein by tyrosine hydroxylase leads to the formation of oligomers","volume":"13","author":"Jin","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1111\/j.1471-4159.2011.07576.x","article-title":"\u03b1-Synuclein oligomers oppose long-term potentiation and impair memory through a calcineurin-dependent mechanism: Relevance to human synucleopathic diseases","volume":"120","author":"Martin","year":"2012","journal-title":"J. Neurochem."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1016\/j.bbr.2017.06.047","article-title":"Brain infusion of \u03b1-synuclein oligomers induces motor and non-motor Parkinson\u2019s disease-like symptoms in mice","volume":"333","author":"Fortuna","year":"2017","journal-title":"Behav. Brain Res."},{"key":"ref_112","doi-asserted-by":"crossref","unstructured":"Boi, L., Pisanu, A., Palmas, M.F., Fusco, G., Carboni, E., Casu, M.A., Satta, V., Scherma, M., Janda, E., and Mocci, I. (2020). Modeling Parkinson\u2019s Disease Neuropathology and Symptoms by Intranigral Inoculation of Preformed Human \u03b1-Synuclein Oligomers. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21228535"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"17497","DOI":"10.1074\/jbc.RA120.013428","article-title":"Fibrillar \u03b1-synuclein toxicity depends on functional lysosomes","volume":"295","author":"Guiney","year":"2020","journal-title":"J. Biol. Chem."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1038\/nature14547","article-title":"\u03b1-Synuclein strains cause distinct synucleinopathies after local and systemic administration","volume":"522","author":"Peelaerts","year":"2015","journal-title":"Nature"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"2851","DOI":"10.1007\/s00018-017-2541-x","article-title":"Synthetic alpha-synuclein fibrils cause mitochondrial impairment and selective dopamine neurodegeneration in part via iNOS-mediated nitric oxide production","volume":"74","author":"Tapias","year":"2017","journal-title":"Cell Mol Life Sci."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"183776","DOI":"10.1016\/j.bbamem.2021.183776","article-title":"A study on the interaction of the amyloid fibrils of \u03b1-synuclein and hen egg white lysozyme with biological membranes","volume":"1864","author":"Zadali","year":"2022","journal-title":"Biochim. Biophys. Acta Biomembr."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"2491","DOI":"10.2174\/13816128113199990497","article-title":"In vivo application of beta amyloid oligomers: A simple tool to evaluate mechanisms of action and new therapeutic approaches","volume":"20","author":"Balducci","year":"2014","journal-title":"Curr. Pharm. Des."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"2295","DOI":"10.1073\/pnas.0911829107","article-title":"Synthetic amyloid-beta oligomers impair long-term memory independently of cellular prion protein","volume":"107","author":"Balducci","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"46363","DOI":"10.1074\/jbc.C400260200","article-title":"Permeabilization of lipid bilayers is a common conformation-dependent activity of soluble amyloid oligomers in protein misfolding diseases","volume":"279","author":"Kayed","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"9686","DOI":"10.1039\/D0CP06456D","article-title":"Conformation-specific perturbation of membrane dynamics by structurally distinct oligomers of Alzheimer\u2019s amyloid-\u03b2 peptide","volume":"23","author":"Madhu","year":"2021","journal-title":"Phys. Chem. Chem. Phys."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"102688","DOI":"10.1016\/j.jbc.2022.102688","article-title":"A penetratin-derived peptide reduces the membrane permeabilization and cell toxicity of \u03b1-synuclein oligomers","volume":"298","author":"Pirhaghi","year":"2022","journal-title":"J. Biol. Chem."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1006\/nbdi.1997.0133","article-title":"A neurotoxic and gliotrophic fragment of the prion protein increases plasma membrane microviscosity","volume":"4","author":"Salmona","year":"1997","journal-title":"Neurobiol. Dis."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1038\/nn.3028","article-title":"The toxic A\u03b2 oligomer and Alzheimer\u2019s disease: An emperor in need of clothes","volume":"15","author":"Benilova","year":"2012","journal-title":"Nat. Neurosci."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"C862","DOI":"10.1152\/ajpcell.00077.2003","article-title":"Channels formed with a mutant prion protein PrP(82-146) homologous to a 7-kDa fragment in diseased brain of GSS patients","volume":"285","author":"Bahadi","year":"2003","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_125","first-page":"E1994","article-title":"Structural characterization of toxic oligomers that are kinetically trapped during \u03b1-synuclein fibril formation","volume":"112","author":"Chen","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1007\/s12035-012-8331-4","article-title":"\u03b1-Synuclein oligomers: An amyloid pore? Insights into mechanisms of \u03b1-synuclein oligomer-lipid interactions","volume":"47","author":"Zijlstra","year":"2013","journal-title":"Mol. Neurobiol."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"2532","DOI":"10.1016\/j.bbamem.2013.06.026","article-title":"Mitochondrial membrane permeabilisation by amyloid aggregates and protection by polyphenols","volume":"1828","author":"Camilleri","year":"2013","journal-title":"Biochim. Biophys. Acta."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"21490","DOI":"10.1074\/jbc.M113.545749","article-title":"Soluble, prefibrillar \u03b1-synuclein oligomers promote complex I-dependent, Ca2+-induced mitochondrial dysfunction","volume":"289","author":"Luth","year":"2014","journal-title":"J. Biol. Chem."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"20710","DOI":"10.1074\/jbc.M110.213538","article-title":"Direct membrane association drives mitochondrial fission by the Parkinson disease-associated protein alpha-synuclein","volume":"286","author":"Nakamura","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"1078550","DOI":"10.3389\/fncel.2023.1078550","article-title":"Alpha-synuclein oligomers alter the spontaneous firing discharge of cultured midbrain neurons","volume":"17","author":"Tomagra","year":"2023","journal-title":"Front. Cell Neurosci."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1007\/s00401-019-02114-9","article-title":"PrP is a central player in toxicity mediated by soluble aggregates of neurodegeneration-causing proteins","volume":"139","author":"Corbett","year":"2020","journal-title":"Acta Neuropathol."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"1569","DOI":"10.1038\/nn.4648","article-title":"\u03b1-synuclein interacts with PrPC to induce cognitive impairment through mGluR5 and NMDAR2B","volume":"20","author":"Ferreira","year":"2017","journal-title":"Nat. Neurosci."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"1614","DOI":"10.1523\/JNEUROSCI.1922-22.2022","article-title":"\u03b1-Synuclein promotes neuronal dysfunction and death by disrupting the binding of ankyrin to \u03b1-Spectrin","volume":"43","author":"Maor","year":"2023","journal-title":"J. Neurosci."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1016\/j.neuron.2017.11.036","article-title":"\u03b1-Synuclein induces mitochondrial dysfunction through spectrin and the actin cytoskeleton","volume":"97","author":"Ordonez","year":"2018","journal-title":"Neuron"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1186\/s13024-022-00560-w","article-title":"LRP1 is a neuronal receptor for \u03b1-synuclein uptake and spread","volume":"17","author":"Chen","year":"2022","journal-title":"Mol. Neurodegener."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1007\/s11302-017-9567-2","article-title":"P2X7 receptor-pannexin 1 interaction mediates extracellular alpha-synuclein-induced ATP release in neuroblastoma SH-SY5Y cells","volume":"13","author":"Wilkaniec","year":"2017","journal-title":"Purinergic. Signal"},{"key":"ref_137","doi-asserted-by":"crossref","unstructured":"Wilkaniec, A., Cie\u015blik, M., Murawska, E., Babiec, L., G\u0105ssowska-Dobrowolska, M., Pa\u0142asz, E., J\u0119\u015bko, H., and Adamczyk, A. (2020). P2X7 Receptor is Involved in Mitochondrial Dysfunction Induced by Extracellular Alpha Synuclein in Neuroblastoma SH-SY5Y Cells. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21113959"},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"1365","DOI":"10.1093\/brain\/awz065","article-title":"Alpha-synuclein targets GluN2A NMDA receptor subunit causing striatal synaptic dysfunction and visuospatial memory alteration","volume":"142","author":"Durante","year":"2019","journal-title":"Brain"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"1261","DOI":"10.3233\/JAD-170819","article-title":"Alzheimer\u2019s Disease, Oligomers, and Inflammation","volume":"62","author":"Forloni","year":"2018","journal-title":"J. Alzheimers. Dis."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"S149","DOI":"10.3233\/JPD-223245","article-title":"Neuroinflammation and Immune Changes in Prodromal Parkinson\u2019s Disease and Other Synucleinopathies","volume":"12","author":"Terkelsen","year":"2022","journal-title":"J. Parkinsons. Dis."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"284","DOI":"10.3389\/fnagi.2019.00284","article-title":"Neuroinflammation and the Gut Microbiota: Possible Alternative Therapeutic Targets to Counteract Alzheimer\u2019s Disease?","volume":"11","author":"Cerovic","year":"2019","journal-title":"Front. Aging Neurosci."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"606069","DOI":"10.3389\/fimmu.2021.606069","article-title":"The Anti-Inflammatory Properties of Phytochemicals and Their Effects on Epigenetic Mechanisms Involved in TLR4\/NF-\u03baB-Mediated Inflammation","volume":"12","author":"Saleh","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1038\/s41577-022-00684-6","article-title":"Inflammation and immune dysfunction in Parkinson disease","volume":"22","author":"Tansey","year":"2022","journal-title":"Nat. Rev. Immunol."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"S129","DOI":"10.3233\/JPD-223241","article-title":"Central and Peripheral Inflammation: Connecting the Immune Responses of Parkinson\u2019s Disease","volume":"12","author":"Williams","year":"2022","journal-title":"J. Parkinsons. Dis."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1016\/bs.pmbts.2022.08.004","article-title":"Human gut microbiota and Parkinson\u2019s disease","volume":"192","author":"Pant","year":"2022","journal-title":"Prog. Mol. Biol. Transl. Sci."},{"key":"ref_146","doi-asserted-by":"crossref","unstructured":"Ryman, S., Vakhtin, A.A., Richardson, S.P., and Lin, H.C. (J. Neurol., 2022). Microbiome-gut-brain dysfunction in prodromal and symptomatic Lewy body diseases, J. Neurol., Epub ahead of print.","DOI":"10.1007\/s00415-022-11461-9"},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1007\/s00401-008-0346-6","article-title":"Applicability of current staging\/categorization of alpha-synuclein pathology and their clinical relevance","volume":"115","author":"Parkkinen","year":"2008","journal-title":"Acta Neuropathol."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.neulet.2005.11.012","article-title":"Gastric alpha-synuclein immunoreactive inclusions in Meissner\u2019s and Auerbach\u2019s plexuses in cases staged for Parkinson\u2019s disease-related brain pathology","volume":"396","author":"Braak","year":"2006","journal-title":"Neurosci. Lett"},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1007\/s00401-014-1343-6","article-title":"Direct evidence of Parkinson pathology spread from the gastrointestinal tract to the brain in rats","volume":"128","author":"Holmqvist","year":"2014","journal-title":"Acta Neuropathol."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.nbd.2018.01.008","article-title":"Induction of alpha-synuclein pathology in the enteric nervous system of the rat and non-human primate results in gastrointestinal dysmotility and transient CNS pathology","volume":"112","author":"Manfredsson","year":"2018","journal-title":"Neurobiol. Dis."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"1833","DOI":"10.3233\/JPD-212733","article-title":"Vagus Nerve and Stomach Synucleinopathy in Parkinson\u2019s Disease, Incidental Lewy Body Disease, and Normal Elderly Subjects: Evidence Against the \u201cBody-First\u201d Hypothesis","volume":"11","author":"Beach","year":"2021","journal-title":"J. Parkinsons. Dis."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1038\/s41531-022-00307-w","article-title":"Redefining the hypotheses driving Parkinson\u2019s diseases research","volume":"8","author":"Farrow","year":"2022","journal-title":"NPJ Parkinsons. Dis."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"1462","DOI":"10.1093\/brain\/awaa096","article-title":"Bidirectional gut-to-brain and brain-to-gut propagation of synucleinopathy in non-human primates","volume":"143","author":"Arotcarena","year":"2020","journal-title":"Brain"},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1016\/j.neuron.2019.05.035","article-title":"Transneuronal Propagation of Pathologic \u03b1-Synuclein from the Gut to the Brain Models Parkinson\u2019s Disease","volume":"103","author":"Kim","year":"2019","journal-title":"Neuron"},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1007\/s00401-019-02040-w","article-title":"Evidence for bidirectional and trans-synaptic parasympathetic and sympathetic propagation of alpha-synuclein in rats","volume":"138","author":"Ferreira","year":"2019","journal-title":"Acta Neuropathol"},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"9262","DOI":"10.1074\/jbc.M109.081125","article-title":"Direct transfer of alpha-synuclein from neuron to astroglia causes inflammatory responses in synucleinopathies","volume":"285","author":"Lee","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"2148","DOI":"10.1038\/s12276-022-00895-w","article-title":"Inflammation promotes synucleinopathy propagation","volume":"54","author":"Kim","year":"2022","journal-title":"Exp. Mol. Med."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"8421","DOI":"10.3390\/ijms21228421","article-title":"Neurodegeneration and Inflammation-An Interesting Interplay in Parkinson\u2019s Disease","volume":"21","author":"Sokratous","year":"2020","journal-title":"Int. J. Mol. Sci."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1007\/s12017-019-08539-5","article-title":"Chronic Mild Gut Inflammation Accelerates Brain Neuropathology and Motor Dysfunction in \u03b1-Synuclein Mutant Mice","volume":"21","author":"Kishimoto","year":"2019","journal-title":"Neuromolecular. Med."},{"key":"ref_160","doi-asserted-by":"crossref","unstructured":"Rossetti, C., and Peri, F. (2021). The Role of Toll-Like Receptor 4 in Infectious and Non Infectious inflammation, Springer.","DOI":"10.1007\/978-3-030-56319-6"},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1016\/j.immuni.2012.10.014","article-title":"Innate immune function by Toll-like receptors: Distinct responses in newborns and the elderly","volume":"37","author":"Kollmann","year":"2012","journal-title":"Immunity"},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"583","DOI":"10.4049\/jimmunol.177.1.583","article-title":"A mechanism for neurodegeneration induced by group B streptococci through activation of the TLR2\/MyD88 pathway in microglia","volume":"177","author":"Lehnardt","year":"2006","journal-title":"J. Immunol."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1080\/14728222.2019.1676416","article-title":"Targeting toll-like receptor 4 to modulate neuroinflammation in central nervous system disorders","volume":"23","author":"Leitner","year":"2019","journal-title":"Expert Opin. Ther. Targets"},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1186\/s12974-014-0166-7","article-title":"The impact of single and pairwise Toll-like receptor activation on neuroinflammation and neurodegeneration","volume":"11","author":"Rosenberger","year":"2014","journal-title":"J. Neuroinflamm."},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"724","DOI":"10.3389\/fimmu.2020.00724","article-title":"TLR4 Cross-Talk with NLRP3 Inflammasome and Complement Signaling Pathways in Alzheimer\u2019s Disease","volume":"11","author":"Yang","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_166","doi-asserted-by":"crossref","unstructured":"Soraci, L., Gambuzza, M.E., Biscetti, L., Lagan\u00e0, P., Lo Russo, C., Buda, A., Barresi, G., Corsonello, A., Lattanzio, F., and Lorello, G. (J. Neurol., 2022). Toll-like receptors and NLRP3 inflammasome-dependent pathways in Parkinson\u2019s disease: Mechanisms and therapeutic implications, J. Neurol., Epub ahead of print.","DOI":"10.1007\/s00415-022-11491-3"},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1042\/EBC20210021","article-title":"Inflammasome activation in neurodegenerative diseases","volume":"65","author":"Ravichandran","year":"2021","journal-title":"Essays Biochem."},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1002\/mds.27874","article-title":"Targeting the microglial NLRP3 inflammasome and its role in Parkinson\u2019s disease","volume":"35","author":"Haque","year":"2020","journal-title":"Mov. Disord."},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"934","DOI":"10.1038\/s41467-019-14189-9","article-title":"Autonomic ganglionic injection of \u03b1-synuclein fibrils as a model of pure autonomic failure \u03b1-synucleinopathy","volume":"11","author":"Wang","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"995","DOI":"10.1002\/mds.26563","article-title":"Serum immune markers and disease progression in an incident Parkinson\u2019s disease cohort (ICICLE-PD)","volume":"31","author":"Wijeyekoon","year":"2016","journal-title":"Mov. Disord."},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1126\/scitranslmed.aah4066","article-title":"Inflammasome inhibition prevents \u03b1-synuclein pathology and dopaminergic neurodegeneration in mice","volume":"10","author":"Gordon","year":"2018","journal-title":"Sci. Transl. Med."},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1146\/annurev-immunol-051116-052358","article-title":"Microglia Function in the Central Nervous System During Health and Neurodegeneration","volume":"35","author":"Colonna","year":"2017","journal-title":"Annu. Rev. Immunol."},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"2143","DOI":"10.4049\/jimmunol.2100035","article-title":"Microglial NLRP3 Inflammasome Activation upon TLR2 and TLR5 Ligation by Distinct \u03b1-Synuclein Assemblies","volume":"207","author":"Scheiblich","year":"2021","journal-title":"J Immunol."},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"643254","DOI":"10.3389\/fphar.2021.643254","article-title":"Neurodegenerative Disease and the NLRP3 Inflammasome","volume":"12","author":"Holbrook","year":"2021","journal-title":"Front. Pharmacol."},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1042\/BJ20150617","article-title":"Amyloid fibrils are the molecular trigger of inflammation in Parkinson\u2019s disease","volume":"471","author":"Gustot","year":"2015","journal-title":"Biochem. J."},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1007\/s00401-015-1504-2","article-title":"Age-dependent defects of alpha-synuclein oligomer uptake in microglia and monocytes","volume":"131","author":"Bliederhaeuser","year":"2016","journal-title":"Acta Neuropathol."},{"key":"ref_177","doi-asserted-by":"crossref","unstructured":"Du, X.Y., Xie, X.X., and Liu, R.T. (2020). The Role of \u03b1-Synuclein Oligomers in Parkinson\u2019s Disease. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21228645"},{"key":"ref_178","doi-asserted-by":"crossref","unstructured":"Lv, Q.K., Tao, K.X., Wang, X.B., Yao, X.Y., Pang, M.Z., Liu, J.Y., Wang, F., and Liu, C.F. (Inflamm. Res., 2023). Role of \u03b1-synuclein in microglia: Autophagy and phagocytosis balance neuroinflammation in Parkinson\u2019s disease, Inflamm. Res., Epub ahead of print.","DOI":"10.1007\/s00011-022-01676-x"},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1016\/j.neurobiolaging.2017.08.023","article-title":"A role of BAG3 in regulating SNCA\/\u03b1-synuclein clearance via selective macroautophagy","volume":"60","author":"Cao","year":"2017","journal-title":"Neurobiol. Aging"},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"1218","DOI":"10.21037\/atm-22-5159","article-title":"BAG3 promotes autophagy and suppresses NLRP3 inflammasome activation in Parkinson\u2019s disease","volume":"10","author":"Ying","year":"2022","journal-title":"Ann. Transl. Med."},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"101806","DOI":"10.1016\/j.pneurobio.2020.101806","article-title":"Microbiota-gut-brain axis in health and disease: Is NLRP3 inflammasome at the crossroads of microbiota-gut-brain communications?","volume":"191","author":"Pellegrini","year":"2020","journal-title":"Prog. Neurobiol."},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.nbd.2012.09.007","article-title":"Colonic inflammation in Parkinson\u2019s disease","volume":"50","author":"Devos","year":"2013","journal-title":"Neurobiol. Dis."},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"S165","DOI":"10.3233\/JPD-213138","article-title":"Inflammatory Animal Models of Parkinson\u2019s Disease","volume":"12","author":"Herrera","year":"2022","journal-title":"J. Parkinsons. Dis."},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1002\/mds.28849","article-title":"Astrocytic Changes in Mitochondrial Oxidative Phosphorylation Protein Levels in Parkinson\u2019s Disease","volume":"37","author":"Chen","year":"2022","journal-title":"Mov. Disord."},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1186\/s40035-021-00265-y","article-title":"Astrocyte dysfunction in Parkinson\u2019s disease: From the perspectives of transmitted \u03b1-synuclein and genetic modulation","volume":"10","author":"Wang","year":"2021","journal-title":"Transl. Neurodegener."},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"3049","DOI":"10.1007\/s12035-017-0529-z","article-title":"Prolonged Dysfunction of Astrocytes and Activation of Microglia Accelerate Degeneration of Dopaminergic Neurons in the Rat Substantia Nigra and Block Compensation of Early Motor Dysfunction Induced by 6-OHDA","volume":"55","author":"Kuter","year":"2018","journal-title":"Mol. Neurobiol."},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1038\/s41531-021-00175-w","article-title":"Astrocytic atrophy as a pathological feature of Parkinson\u2019s disease with LRRK2 mutation","volume":"7","author":"Mato","year":"2021","journal-title":"NPJ Parkinsons. Dis."},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1038\/s41583-022-00641-1","article-title":"Astrocyte contribution to dysfunction, risk and progression in neurodegenerative disorders","volume":"24","author":"Brandebura","year":"2023","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1136\/jnnp-2019-322338","article-title":"Parkinson\u2019s disease: Etiopathogenesis and treatment","volume":"91","author":"Jankovic","year":"2020","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1038\/35006074","article-title":"A Drosophila model of Parkinson\u2019s disease","volume":"404","author":"Feany","year":"2000","journal-title":"Nature"},{"key":"ref_191","doi-asserted-by":"crossref","first-page":"2683","DOI":"10.1021\/acschemneuro.9b00092","article-title":"Identification of a New \u03b1-Synuclein Aggregation Inhibitor via Mass Spectrometry Based Screening","volume":"10","author":"Xu","year":"2019","journal-title":"ACS Chem. Neurosci."},{"key":"ref_192","doi-asserted-by":"crossref","first-page":"1185","DOI":"10.1038\/nm1102-1185","article-title":"Pharmacological prevention of Parkinson disease in Drosophila","volume":"8","author":"Auluck","year":"2002","journal-title":"Nat. Med."},{"key":"ref_193","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1126\/science.1067389","article-title":"Chaperone suppression of alpha-synuclein toxicity in a Drosophila model for Parkinson\u2019s disease","volume":"295","author":"Auluck","year":"2002","journal-title":"Science"},{"key":"ref_194","doi-asserted-by":"crossref","first-page":"1106","DOI":"10.1042\/BST0331106","article-title":"Alpha-synuclein aggregation in neurodegenerative diseases and its inhibition as a potential therapeutic strategy","volume":"33","author":"Paleologou","year":"2005","journal-title":"Biochem. Soc. Trans."},{"key":"ref_195","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1007\/s12031-002-0012-8","article-title":"Development of a new treatment for Alzheimer\u2019s disease and Parkinson\u2019s disease using anti-aggregatory beta-synuclein-derived peptides","volume":"19","author":"Windisch","year":"2002","journal-title":"J. Mol. Neurosci."},{"key":"ref_196","doi-asserted-by":"crossref","unstructured":"Vidovi\u0107, M., and Rikalovic, M.G. (2022). Alpha-Synuclein Aggregation Pathway in Parkinson\u2019s Disease: Current Status and Novel Therapeutic Approaches. Cells, 11.","DOI":"10.3390\/cells11111732"},{"key":"ref_197","doi-asserted-by":"crossref","first-page":"6085","DOI":"10.1021\/bi0600749","article-title":"Small molecule inhibitors of alpha-synuclein filament assembly","volume":"45","author":"Masuda","year":"2006","journal-title":"Biochemistry"},{"key":"ref_198","doi-asserted-by":"crossref","unstructured":"Pujols, J., Pe\u00f1a-D\u00edaz, S., Conde-Gim\u00e9nez, M., Pinheiro, F., Navarro, S., Sancho, J., and Ventura, S. (2017). High-Throughput Screening Methodology to Identify Alpha-Synuclein Aggregation Inhibitors. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18030478"},{"key":"ref_199","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1038\/nm0602-600","article-title":"Dopamine-dependent neurotoxicity of alpha-synuclein: A mechanism for selective neurodegeneration in Parkinson disease","volume":"8","author":"Xu","year":"2002","journal-title":"Nat. Med."},{"key":"ref_200","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1038\/s41598-021-04131-9","article-title":"Two-step screening method to identify \u03b1-synuclein aggregation inhibitors for Parkinson\u2019s disease","volume":"12","author":"Hideshima","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_201","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1016\/j.slasd.2022.05.001","article-title":"A novel high-throughput screening strategy for targeting alpha-synuclein and other long-lived proteins","volume":"27","author":"Casalino","year":"2022","journal-title":"SLAS Discov."},{"key":"ref_202","doi-asserted-by":"crossref","unstructured":"De Luca, L., Vittorio, S., Pe\u00f1a-D\u00edaz, S., Pitasi, G., Fornt-Su\u00f1\u00e9, M., Bucolo, F., Ventura, S., and Gitto, R. (2022). Ligand-Based Discovery of a Small Molecule as Inhibitor of \u03b1-Synuclein Amyloid Formation. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232314844"},{"key":"ref_203","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1124\/pharmrev.120.000133","article-title":"Therapeutics in the Pipeline Targeting \u03b1-Synuclein for Parkinson\u2019s Disease","volume":"74","author":"Oh","year":"2022","journal-title":"Pharmacol. Rev."},{"key":"ref_204","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1007\/s00401-013-1114-9","article-title":"Anle138b: A novel oligomer modulator for disease-modifying therapy of neurodegenerative diseases such as prion and Parkinson\u2019s disease","volume":"125","author":"Wagner","year":"2013","journal-title":"Acta Neuropathol."},{"key":"ref_205","doi-asserted-by":"crossref","first-page":"5385","DOI":"10.1038\/s41467-022-32797-w","article-title":"The clinical drug candidate anle138b binds in a cavity of lipidic \u03b1-synuclein fibrils","volume":"13","author":"Antonschmidt","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_206","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1007\/s00401-014-1265-3","article-title":"The oligomer modulator anle138b inhibits disease progression in a Parkinson mouse model even with treatment started after disease onset","volume":"127","author":"Levin","year":"2014","journal-title":"Acta Neuropathol."},{"key":"ref_207","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1007\/s00401-019-02023-x","article-title":"Depopulation of dense \u03b1-synuclein aggregates is associated with rescue of dopamine neuron dysfunction and death in a new Parkinson\u2019s disease model","volume":"138","author":"Wegrzynowicz","year":"2019","journal-title":"Acta Neuropathol."},{"key":"ref_208","doi-asserted-by":"crossref","first-page":"99","DOI":"10.3389\/fnins.2016.00099","article-title":"Anle138b Partly Ameliorates Motor Deficits Despite Failure of Neuroprotection in a Model of Advanced Multiple System Atrophy","volume":"10","author":"Fellner","year":"2016","journal-title":"Front. Neurosci."},{"key":"ref_209","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1002\/mds.27562","article-title":"Anle138b modulates \u03b1-synuclein oligomerization and prevents motor decline and neurodegeneration in a mouse model of multiple system atrophy","volume":"34","author":"Weckbecker","year":"2019","journal-title":"Mov. Disord."},{"key":"ref_210","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1186\/s40035-020-00217-y","article-title":"Targeting \u03b1-synuclein by PD03 AFFITOPE\u00ae and Anle138b rescues neurodegenerative pathology in a model of multiple system atrophy: Clinical relevance","volume":"9","author":"Lemos","year":"2020","journal-title":"Transl. Neurodegener"},{"key":"ref_211","doi-asserted-by":"crossref","first-page":"104021","DOI":"10.1016\/j.ebiom.2022.104021","article-title":"Safety, tolerability and pharmacokinetics of the oligomer modulator anle138b with exposure levels sufficient for therapeutic efficacy in a murine Parkinson model: A randomised, double-blind, placebo-controlled phase 1a trial","volume":"80","author":"Levin","year":"2022","journal-title":"EBioMedicine"},{"key":"ref_212","doi-asserted-by":"crossref","first-page":"2380","DOI":"10.1021\/acschemneuro.2c00355","article-title":"Phosphatidylcholine and Phosphatidylserine Uniquely Modify the Secondary Structure of \u03b1-Synuclein Oligomers Formed in Their Presence at the Early Stages of Protein Aggregation","volume":"13","author":"Dou","year":"2022","journal-title":"ACS Chem. Neurosci."},{"key":"ref_213","doi-asserted-by":"crossref","first-page":"680026","DOI":"10.3389\/fnins.2021.680026","article-title":"Squalamine and Its Derivatives Modulate the Aggregation of Amyloid-\u03b2 and \u03b1-Synuclein and Suppress the Toxicity of Their Oligomers","volume":"15","author":"Limbocker","year":"2021","journal-title":"Front. Neurosci."},{"key":"ref_214","doi-asserted-by":"crossref","first-page":"E1009","DOI":"10.1073\/pnas.1610586114","article-title":"A natural product inhibits the initiation of \u03b1-synuclein aggregation and suppresses its toxicity","volume":"114","author":"Perni","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_215","doi-asserted-by":"crossref","first-page":"1477","DOI":"10.3233\/JPD-202076","article-title":"Squalamine Restores the Function of the Enteric Nervous System in Mouse Models of Parkinson\u2019s Disease","volume":"10","author":"West","year":"2020","journal-title":"J. Parkinsons. Dis."},{"key":"ref_216","doi-asserted-by":"crossref","first-page":"1666","DOI":"10.7326\/M22-1438","article-title":"Oral ENT-01 Targets Enteric Neurons to Treat Constipation in Parkinson Disease: A Randomized Controlled Trial","volume":"175","author":"Camilleri","year":"2022","journal-title":"Ann. Intern. Med."},{"key":"ref_217","doi-asserted-by":"crossref","first-page":"742","DOI":"10.1039\/D1NP00042J","article-title":"Squalamine and trodusquemine: Two natural products for neurodegenerative diseases, from physical chemistry to the clinic","volume":"39","author":"Limbocker","year":"2022","journal-title":"Nat. Prod. Rep."},{"key":"ref_218","doi-asserted-by":"crossref","first-page":"2308","DOI":"10.1021\/acschembio.8b00466","article-title":"Multistep Inhibition of \u03b1-Synuclein Aggregation and Toxicity in Vitro and in Vivo by Trodusquemine","volume":"13","author":"Perni","year":"2018","journal-title":"ACS Chem. Biol."},{"key":"ref_219","doi-asserted-by":"crossref","first-page":"113115","DOI":"10.1016\/j.colsurfb.2022.113115","article-title":"Reorganization of the outer layer of a model of the plasma membrane induced by a neuroprotective aminosterol","volume":"222","author":"Barletti","year":"2022","journal-title":"Colloids Surf. B Biointerfaces"},{"key":"ref_220","doi-asserted-by":"crossref","first-page":"166706","DOI":"10.1016\/j.jmb.2020.11.005","article-title":"The Library Derived 4554W Peptide Inhibits Primary Nucleation of \u03b1-Synuclein","volume":"432","author":"Meade","year":"2020","journal-title":"J. Mol. Biol."},{"key":"ref_221","doi-asserted-by":"crossref","first-page":"e46775","DOI":"10.7554\/eLife.46775","article-title":"Inhibition of synucleinopathic seeding by rationally designed inhibitors","volume":"9","author":"Sangwan","year":"2020","journal-title":"Elife"},{"key":"ref_222","doi-asserted-by":"crossref","first-page":"822","DOI":"10.1038\/nm0798-822","article-title":"Beta-sheet breaker peptides inhibit fibrillogenesis in a rat brain model of amyloidosis: Implications for Alzheimer\u2019s therapy","volume":"4","author":"Soto","year":"1998","journal-title":"Nat. Med."},{"key":"ref_223","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1016\/S0140-6736(99)11419-3","article-title":"Reversion of prion protein conformational changes by synthetic beta-sheet breaker peptides","volume":"355","author":"Soto","year":"2000","journal-title":"Lancet"},{"key":"ref_224","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1038\/s42003-021-01746-6","article-title":"Development of an \u03b1-synuclein knockdown peptide and evaluation of its efficacy in Parkinson\u2019s disease models","volume":"4","author":"Jin","year":"2021","journal-title":"Commun. Biol."},{"key":"ref_225","doi-asserted-by":"crossref","first-page":"108614","DOI":"10.1016\/j.abb.2020.108614","article-title":"Sequence and structure-based peptides as potent amyloid inhibitors: A review","volume":"695","author":"Mitra","year":"2020","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_226","doi-asserted-by":"crossref","first-page":"659926","DOI":"10.3389\/fnmol.2021.659926","article-title":"Identification of Two Novel Peptides that Inhibit \u03b1-Synuclein Toxicity and Aggregation","volume":"14","author":"Popova","year":"2021","journal-title":"Front. Mol. Neurosci."},{"key":"ref_227","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1002\/mds.26878","article-title":"First-in-human assessment of PRX002, an anti-\u03b1-synuclein monoclonal antibody, in healthy volunteers","volume":"32","author":"Schenk","year":"2017","journal-title":"Mov. Disord."},{"key":"ref_228","doi-asserted-by":"crossref","first-page":"982","DOI":"10.1038\/35050116","article-title":"A beta peptide vaccination prevents memory loss in an animal model of Alzheimer\u2019s disease","volume":"408","author":"Morgan","year":"2000","journal-title":"Nature"},{"key":"ref_229","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1056\/NEJMoa2212948","article-title":"Lecanemab in Early Alzheimer\u2019s Disease","volume":"388","author":"Swanson","year":"2023","journal-title":"N. Engl. J. Med."},{"key":"ref_230","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1016\/j.neuron.2005.05.010","article-title":"Effects of alpha-synuclein immunization in a mouse model of Parkinson\u2019s disease","volume":"46","author":"Masliah","year":"2005","journal-title":"Neuron"},{"key":"ref_231","doi-asserted-by":"crossref","unstructured":"Masliah, E., Rockenstein, E., Mante, M., Crews, L., Spencer, B., Adame, A., Patrick, C., Trejo, M., Ubhi, K., and Rohn, T.T. (2011). Passive immunization reduces behavioral and neuropathological deficits in an alpha-synuclein transgenic model of Lewy body disease. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0019338"},{"key":"ref_232","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1007\/s00401-014-1256-4","article-title":"Next-generation active immunization approach for synucleinopathies: Implications for Parkinson\u2019s disease clinical trials","volume":"127","author":"Mandler","year":"2014","journal-title":"Acta Neuropathol."},{"key":"ref_233","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1016\/S1474-4422(20)30136-8","article-title":"Safety and immunogenicity of the \u03b1-synuclein active immunotherapeutic PD01A in patients with Parkinson\u2019s disease: A randomised, single-blinded, phase 1 trial","volume":"19","author":"Volc","year":"2020","journal-title":"Lancet Neurol."},{"key":"ref_234","doi-asserted-by":"crossref","first-page":"1957","DOI":"10.1002\/mds.28218","article-title":"A Phase 1 Randomized Trial of Specific Active \u03b1-Synuclein Immunotherapies PD01A and PD03A in Multiple System Atrophy","volume":"35","author":"Meissner","year":"2020","journal-title":"Mov. Disord."},{"key":"ref_235","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.3233\/JPD-212594","article-title":"Safety and Tolerability of Active Immunotherapy Targeting \u03b1-Synuclein with PD03A in Patients with Early Parkinson\u2019s Disease: A Randomized, Placebo-Controlled, Phase 1 Study","volume":"11","author":"Poewe","year":"2021","journal-title":"J. Parkinsons. Dis."},{"key":"ref_236","doi-asserted-by":"crossref","first-page":"1416","DOI":"10.1002\/mds.29016","article-title":"A Randomized First-in-Human Study with UB-312, a UBITh\u00ae \u03b1-Synuclein Peptide Vaccine","volume":"37","author":"Yu","year":"2022","journal-title":"Mov. Disord."},{"key":"ref_237","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1186\/s13195-020-00727-x","article-title":"Novel antibodies detect additional \u03b1-synuclein pathology in synucleinopathies: Potential development for immunotherapy","volume":"12","author":"Nimmo","year":"2020","journal-title":"Alzheimers Res. Ther."},{"key":"ref_238","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1007\/s00401-021-02381-5","article-title":"Immunisation with UB-312 in the Thy1SNCA mouse prevents motor performance deficits and oligomeric \u03b1-synuclein accumulation in the brain and gut","volume":"143","author":"Nimmo","year":"2022","journal-title":"Acta Neuropathol."},{"key":"ref_239","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1038\/22124","article-title":"Immunization with amyloid-beta attenuates Alzheimer-disease-like pathology in the PDAPP mouse","volume":"400","author":"Schenk","year":"1999","journal-title":"Nature"},{"key":"ref_240","doi-asserted-by":"crossref","first-page":"1206","DOI":"10.1001\/jamaneurol.2018.1487","article-title":"Safety and Tolerability of Multiple Ascending Doses of PRX002\/RG7935, an Anti-\u03b1-Synuclein Monoclonal Antibody, in Patients with Parkinson Disease: A Randomized Clinical Trial","volume":"75","author":"Jankovic","year":"2018","journal-title":"JAMA Neurol."},{"key":"ref_241","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1056\/NEJMoa2202867","article-title":"Trial of Prasinezumab in Early-Stage Parkinson\u2019s Disease","volume":"387","author":"Pagano","year":"2022","journal-title":"N. Engl. J. Med."},{"key":"ref_242","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1038\/nature19323","article-title":"The antibody aducanumab reduces A\u03b2 plaques in Alzheimer\u2019s disease","volume":"537","author":"Sevigny","year":"2016","journal-title":"Nature"},{"key":"ref_243","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1016\/j.nbd.2018.10.016","article-title":"Development of an aggregate-selective, human-derived \u03b1-synuclein antibody BIIB054 that ameliorates disease phenotypes in Parkinson\u2019s disease models","volume":"124","author":"Weihofen","year":"2019","journal-title":"Neurobiol. Dis."},{"key":"ref_244","doi-asserted-by":"crossref","first-page":"1154","DOI":"10.1002\/mds.27738","article-title":"Randomized phase I clinical trial of anti-\u03b1-synuclein antibody BIIB054","volume":"34","author":"Brys","year":"2019","journal-title":"Mov. Disord."},{"key":"ref_245","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1056\/NEJMoa2203395","article-title":"Trial of Cinpanemab in Early Parkinson\u2019s Disease","volume":"387","author":"Lang","year":"2022","journal-title":"N. Engl. J. Med."},{"key":"ref_246","doi-asserted-by":"crossref","first-page":"104582","DOI":"10.1016\/j.nbd.2019.104582","article-title":"Preclinical development of a high affinity \u03b1-synuclein antibody, MEDI1341, that can enter the brain, sequester extracellular \u03b1-synuclein and attenuate \u03b1-synuclein spreading in vivo","volume":"132","author":"Schofield","year":"2019","journal-title":"Neurobiol. Dis."},{"key":"ref_247","doi-asserted-by":"crossref","first-page":"105969","DOI":"10.1016\/j.nbd.2022.105969","article-title":"Anti-\u03b1-synuclein c-terminal antibodies block PFF uptake and accumulation of phospho-synuclein in preclinical models of Parkinson\u2019s disease","volume":"177","author":"Brendza","year":"2022","journal-title":"Neurobiol. Dis."},{"key":"ref_248","doi-asserted-by":"crossref","unstructured":"Jensen, P.H., Schlossmacher, M.G., and Stefanis, L. (Mov. Disord., 2023). Who Ever Said It Would Be Easy? Reflecting on Two Clinical Trials Targeting \u03b1-Synuclein, Mov. Disord., Epub ahead of print.","DOI":"10.1002\/mds.29318"},{"key":"ref_249","doi-asserted-by":"crossref","first-page":"e000079","DOI":"10.1136\/bmjno-2020-000079","article-title":"Alzheimer\u2019s disease: From basic science to precision medicine approach","volume":"2","author":"Forloni","year":"2020","journal-title":"BMJ Neurol. Open."},{"key":"ref_250","doi-asserted-by":"crossref","first-page":"3980","DOI":"10.1007\/s12035-022-02824-4","article-title":"Binding Stability of Antibody-\u03b1-Synuclein Complexes Predicts the Protective Efficacy of Anti-\u03b1-synuclein Antibodies","volume":"59","author":"Wolff","year":"2022","journal-title":"Mol. Neurobiol."},{"key":"ref_251","doi-asserted-by":"crossref","first-page":"2117","DOI":"10.3233\/JPD-223290","article-title":"Role of NLRP3 Inflammasome in Parkinson\u2019s Disease and Therapeutic Considerations","volume":"12","author":"Nguyen","year":"2022","journal-title":"J. Parkinsons. Dis."},{"key":"ref_252","doi-asserted-by":"crossref","first-page":"5382","DOI":"10.1038\/s41467-021-25767-1","article-title":"Selective targeting of the TLR2\/MyD88\/NF-\u03baB pathway reduces \u03b1-synuclein spreading in vitro and in vivo","volume":"12","author":"Dutta","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_253","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1038\/s41420-021-00676-w","article-title":"Phosphorylated \u03b1-synuclein aggregated in Schwann cells exacerbates peripheral neuroinflammation and nerve dysfunction in Parkinson\u2019s disease through TLR2\/NF-\u03baB pathway","volume":"7","author":"Sun","year":"2021","journal-title":"Cell Death Discov."},{"key":"ref_254","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1016\/j.jid.2015.12.024","article-title":"Staphylococcal LTA-Induced miR-143 Inhibits Propionibacterium acnes-Mediated Inflammatory Response in Skin","volume":"136","author":"Xia","year":"2016","journal-title":"J. Investig. Dermatol."},{"key":"ref_255","doi-asserted-by":"crossref","first-page":"1562","DOI":"10.1038\/ncomms2534","article-title":"Neuron-released oligomeric \u03b1-synuclein is an endogenous agonist of TLR2 for paracrine activation of microglia","volume":"4","author":"Kim","year":"2013","journal-title":"Nat. Commun."},{"key":"ref_256","doi-asserted-by":"crossref","first-page":"4203","DOI":"10.1021\/acschemneuro.0c00480","article-title":"\u03b1-Synuclein Exhibits Differential Membrane Perturbation, Nucleation, and TLR2 Binding through Its Secondary Structure","volume":"11","author":"Kumari","year":"2020","journal-title":"ACS Chem. Neurosci."},{"key":"ref_257","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1016\/j.celrep.2015.09.044","article-title":"Antagonizing Neuronal Toll-like Receptor 2 Prevents Synucleinopathy by Activating Autophagy","volume":"13","author":"Kim","year":"2015","journal-title":"Cell Rep."},{"key":"ref_258","doi-asserted-by":"crossref","first-page":"547","DOI":"10.5607\/en.2019.28.5.547","article-title":"Targeting Microglial and Neuronal Toll-like Receptor 2 in Synucleinopathies","volume":"28","author":"Kwon","year":"2019","journal-title":"Exp. Neurobiol."},{"key":"ref_259","doi-asserted-by":"crossref","first-page":"102260","DOI":"10.1016\/j.jbc.2022.102260","article-title":"A small molecule toll-like receptor antagonist rescues \u03b1-synuclein fibril pathology","volume":"298","author":"Chedid","year":"2022","journal-title":"J. Biol. Chem."},{"key":"ref_260","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.bbi.2019.06.042","article-title":"Toll-like receptors and their therapeutic potential in Parkinson\u2019s disease and \u03b1-synucleinopathies","volume":"81","author":"Kouli","year":"2019","journal-title":"Brain Behav. Imm."},{"key":"ref_261","doi-asserted-by":"crossref","first-page":"2024","DOI":"10.1093\/brain\/awab122","article-title":"Reactive microglia enhance the transmission of exosomal \u03b1-synuclein via toll-like receptor 2","volume":"144","author":"Xia","year":"2021","journal-title":"Brain"},{"key":"ref_262","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1016\/j.neurobiolaging.2018.06.002","article-title":"Doxycycline counteracts neuroinflammation restoring memory in Alzheimer\u2019s disease mouse models","volume":"70","author":"Balducci","year":"2018","journal-title":"Neurobiol. Agin."},{"key":"ref_263","doi-asserted-by":"crossref","first-page":"10849","DOI":"10.1073\/pnas.162195499","article-title":"Tetracyclines affect prion infectivity","volume":"99","author":"Forloni","year":"2002","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_264","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1016\/S1474-4422(13)70307-7","article-title":"Doxycycline in Creutzfeldt-Jakob disease: A phase 2, randomised, double-blind, placebo-controlled trial","volume":"13","author":"Marcon","year":"2014","journal-title":"Lancet Neurol."},{"key":"ref_265","doi-asserted-by":"crossref","first-page":"738","DOI":"10.3389\/fphar.2019.00738","article-title":"Doxycycline for Alzheimer\u2019s Disease: Fighting \u03b2-Amyloid Oligomers and Neuroinflammation","volume":"10","author":"Balducci","year":"2019","journal-title":"Front. Pharmacol."},{"key":"ref_266","doi-asserted-by":"crossref","first-page":"105229","DOI":"10.1016\/j.parkreldis.2022.105229","article-title":"Repositioning Doxycycline for treating Parkinson\u2019s Disease: Evidence from a pre-clinical mouse model","volume":"106","author":"Artioli","year":"2023","journal-title":"Parkinsonism. Relat. Dis."},{"key":"ref_267","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1016\/j.bbi.2016.10.012","article-title":"Toll-like receptor 4-dependent glial cell activation mediates the impairment in memory establishment induced by \u03b2-amyloid oligomers in an acute mouse model of Alzheimer\u2019s disease","volume":"60","author":"Balducci","year":"2017","journal-title":"Brain Behav. Immun."},{"key":"ref_268","doi-asserted-by":"crossref","first-page":"1309","DOI":"10.1006\/jmbi.2000.3840","article-title":"Tetracycline affects abnormal properties of synthetic PrP peptides and PrP(Sc) in vitro","volume":"300","author":"Tagliavini","year":"2000","journal-title":"J. Mol. Biol."},{"key":"ref_269","doi-asserted-by":"crossref","first-page":"41755","DOI":"10.1038\/srep41755","article-title":"Repurposing doxycycline for synucleinopathies: Remodelling of \u03b1-synuclein oligomers towards non-toxic parallel beta-sheet structured species","volume":"7","author":"Barbosa","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_270","doi-asserted-by":"crossref","first-page":"105256","DOI":"10.1016\/j.nbd.2021.105256","article-title":"Doxycycline inhibits \u03b1-synuclein-associated pathologies in vitro and in vivo","volume":"151","author":"Parrales","year":"2021","journal-title":"Neurobiol. Dis."},{"key":"ref_271","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/bs.pmbts.2020.11.001","article-title":"Inflammation and Parkinson\u2019s disease pathogenesis: Mechanisms and therapeutic insight","volume":"177","author":"Forloni","year":"2021","journal-title":"Prog. Mol. Biol. Transl. Sci."},{"key":"ref_272","doi-asserted-by":"crossref","first-page":"1045465","DOI":"10.3389\/fphar.2022.1045465","article-title":"Doxycycline attenuates l-DOPA-induced dyskinesia through an anti-inflammatory effect in a hemiparkinsonian mouse model","volume":"13","author":"Bortolanza","year":"2022","journal-title":"Front. Pharmacol."},{"key":"ref_273","doi-asserted-by":"crossref","first-page":"1403","DOI":"10.1007\/s00702-018-1913-1","article-title":"Tetracycline repurposing in neurodegeneration: Focus on Parkinson\u2019s disease","volume":"125","author":"Bortolanza","year":"2018","journal-title":"J. Neural. Transm."},{"key":"ref_274","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1080\/19336896.2015.1027857","article-title":"Preventive study in subjects at risk of FFI: Innovative approach to rare diseases","volume":"9","author":"Forloni","year":"2015","journal-title":"Prion"},{"key":"ref_275","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1080\/19336896.2022.2083435","article-title":"Preventive pharmacological treatment in subjects at risk for fatal familial insomnia: Science and public engagement","volume":"16","author":"Forloni","year":"2022","journal-title":"Prion"},{"key":"ref_276","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1124\/jpet.118.252064","article-title":"Plasma and Brain Concentrations of Doxycycline after Single and Repeated Doses in Wild-Type and APP23 Mice","volume":"368","author":"Lucchetti","year":"2019","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_277","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1007\/s00702-021-02427-8","article-title":"Disease-modifying treatment of Parkinson\u2019s disease by phytochemicals: Targeting multiple pathogenic factors","volume":"129","author":"Naoi","year":"2022","journal-title":"J. Neural. Transm."},{"key":"ref_278","doi-asserted-by":"crossref","first-page":"115859","DOI":"10.1016\/j.taap.2021.115859","article-title":"Roflupram attenuates \u03b1-synuclein-induced cytotoxicity and promotes the mitochondrial translocation of Parkin in SH-SY5Y cells overexpressing A53T mutant \u03b1-synuclein","volume":"436","author":"Zhong","year":"2022","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_279","doi-asserted-by":"crossref","unstructured":"Umeda, T., Hatanaka, Y., Sakai, A., and Tomiyama, T. (2021). Nasal Rifampicin Improves Cognition in a Mouse Model of Dementia with Lewy Bodies by Reducing \u03b1-Synuclein Oligomers. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22168453"},{"key":"ref_280","doi-asserted-by":"crossref","first-page":"1544","DOI":"10.1080\/01480545.2020.1846549","article-title":"Rifampicin decreases neuroinflammation to maintain mitochondrial function and calcium homeostasis in rotenone-treated zebrafish","volume":"45","author":"Yurtsever","year":"2022","journal-title":"Drug Chem. Toxicol."},{"key":"ref_281","doi-asserted-by":"crossref","first-page":"1473","DOI":"10.4103\/1673-5374.274336","article-title":"Rifampicin quinone pretreatment improves neuronal survival by modulating microglia inflammation induced by \u03b1-synuclein","volume":"15","year":"2020","journal-title":"Neural Regen. Res."},{"key":"ref_282","doi-asserted-by":"crossref","unstructured":"Acu\u00f1a, L., Hamadat, S., Corbal\u00e1n, N.S., Gonz\u00e1lez-Liz\u00e1rraga, F., Dos-Santos-Pereira, M., Rocca, J., D\u00edaz, J.S., Del-Bel, E., Papy-Garc\u00eda, D., and Cheh\u00edn, R.N. (2019). Rifampicin and Its Derivative Rifampicin Quinone Reduce Microglial Inflammatory Responses and Neurodegeneration Induced In Vitro by \u03b1-Synuclein Fibrillary Aggregates. Cells, 8.","DOI":"10.3390\/cells8080776"},{"key":"ref_283","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1080\/01616412.2020.1866353","article-title":"Rifampicin ameliorates lipopolysaccharide-induced cognitive and motor impairments via inhibition of the TLR4\/MyD88\/NF-\u03baB signaling pathway in mice","volume":"43","author":"Bi","year":"2021","journal-title":"Neurol. Res."},{"key":"ref_284","doi-asserted-by":"crossref","first-page":"104690","DOI":"10.1016\/j.tiv.2019.104690","article-title":"Rifampicin attenuates rotenone-treated microglia inflammation via improving lysosomal function","volume":"63","author":"Liang","year":"2020","journal-title":"Toxicol. In Vitro"},{"key":"ref_285","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.brainres.2011.04.019","article-title":"Rifampicin inhibits microglial inflammation and improves neuron survival against inflammation","volume":"13","author":"Bi","year":"2011","journal-title":"Brain Res."},{"key":"ref_286","doi-asserted-by":"crossref","first-page":"S82","DOI":"10.1016\/j.parkreldis.2015.09.038","article-title":"Interventional trials in atypical parkinsonism","volume":"22","author":"Krismer","year":"2016","journal-title":"Parkinsonism. Relat. Disord."},{"key":"ref_287","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1007\/s10286-015-0281-2","article-title":"Optimizing clinical trial design for multiple system atrophy: Lessons from the rifampicin study","volume":"25","author":"Singer","year":"2015","journal-title":"Clin. Auton. Res."},{"key":"ref_288","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1111\/pcn.12637","article-title":"Therapeutic role of rifampicin in Alzheimer\u2019s disease","volume":"72","author":"Yulug","year":"2018","journal-title":"Psychiatry Clin. Neurosci."},{"key":"ref_289","doi-asserted-by":"crossref","first-page":"2397","DOI":"10.3233\/JPD-223516","article-title":"Molecular Mechanisms Mediating the Transfer of Disease-Associated Proteins and Effects on Neuronal Activity","volume":"12","author":"Khani","year":"2022","journal-title":"J. Parkinsons. Dis."},{"key":"ref_290","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1186\/s13024-018-0276-2","article-title":"Immunotherapy targeting toll-like receptor 2 alleviates neurodegeneration in models of synucleinopathy by modulating \u03b1-synuclein transmission and neuroinflammation","volume":"13","author":"Kim","year":"2018","journal-title":"Mol. Neurodegener."},{"key":"ref_291","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1002\/mds.28399","article-title":"Immunohistochemical Detection of Synuclein Pathology in Skin in Idiopathic Rapid Eye Movement Sleep Behavior Disorder and Parkinsonism","volume":"36","author":"Tsao","year":"2021","journal-title":"Mov. Disord."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/6\/5914\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:59:27Z","timestamp":1760122767000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/6\/5914"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,21]]},"references-count":291,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2023,3]]}},"alternative-id":["ijms24065914"],"URL":"https:\/\/doi.org\/10.3390\/ijms24065914","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,3,21]]}}}