{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T03:18:59Z","timestamp":1791343139206,"version":"4.3.1"},"reference-count":113,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2022,1,16]],"date-time":"2022-01-16T00:00:00Z","timestamp":1642291200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>\u03b1-Synuclein (\u03b1S) is a small, unstructured, presynaptic protein expressed in the brain. Its aggregated form is a major component of Lewy bodies, the large proteinaceous deposits in Parkinson\u2019s disease. The closely related protein, \u03b2-Synuclein (\u03b2S), is co-expressed with \u03b1S. In vitro, \u03b2S acts as a molecular chaperone to inhibit \u03b1S aggregation. As a result of this assignation, \u03b2S has been largely understudied in comparison to \u03b1S. However, recent reports suggest that \u03b2S promotes neurotoxicity, implying that \u03b2S is involved in other cellular pathways with functions independent of \u03b1S. Here, we review the current literature pertaining to human \u03b2S in order to understand better the role of \u03b2S in homeostasis and pathology. Firstly, the structure of \u03b2S is discussed. Secondly, the ability of \u03b2S to (i) act as a molecular chaperone; (ii) regulate synaptic function, lipid binding, and the nigrostriatal dopaminergic system; (iii) mediate apoptosis; (iv) participate in protein degradation pathways; (v) modulate intracellular metal levels; and (vi) promote cellular toxicity and protein aggregation is explored. Thirdly, the P123H and V70M mutations of \u03b2S, which are associated with dementia with Lewy bodies, are discussed. Finally, the importance of post-translational modifications on the structure and function of \u03b2S is reviewed. Overall, it is concluded that \u03b2S has both synergistic and antagonistic interactions with \u03b1S, but it may also possess important cellular functions independent of \u03b1S.<\/jats:p>","DOI":"10.3390\/biom12010142","type":"journal-article","created":{"date-parts":[[2022,1,16]],"date-time":"2022-01-16T20:44:00Z","timestamp":1642365840000},"page":"142","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":42,"title":["\u03b2-Synuclein: An Enigmatic Protein with Diverse Functionality"],"prefix":"10.3390","volume":"12","author":[{"given":"Junna","family":"Hayashi","sequence":"first","affiliation":[{"name":"Research School of Chemistry, The Australian National University, Acton, ACT 2601, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2441-8108","authenticated-orcid":false,"given":"John A.","family":"Carver","sequence":"additional","affiliation":[{"name":"Research School of Chemistry, The Australian National University, Acton, ACT 2601, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,1,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1038\/nrm3920","article-title":"Intrinsically disordered proteins in cellular signalling and regulation","volume":"16","author":"Wright","year":"2014","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e0217889","DOI":"10.1371\/journal.pone.0217889","article-title":"Intrinsically disordered proteins and structured proteins with intrinsically disordered regions have different functional roles in the cell","volume":"14","author":"Deiana","year":"2019","journal-title":"PLoS ONE"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2433","DOI":"10.1016\/j.febslet.2015.06.003","article-title":"Functional advantages of dynamic protein disorder","volume":"589","author":"Berlow","year":"2015","journal-title":"FEBS Lett."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"9730","DOI":"10.1021\/jacs.6b06543","article-title":"Finding our way in the dark proteome","volume":"138","author":"Bhowmick","year":"2016","journal-title":"J. Am. Chem. Soc."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1146\/annurev.biophys.37.032807.125924","article-title":"Intrinsically disordered proteins in human diseases: Introducing the D2 concept","volume":"37","author":"Uversky","year":"2008","journal-title":"Annu. Rev. Biophys."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2626","DOI":"10.1039\/C4MB00290C","article-title":"Proteome-wide analysis of human disease mutations in short linear motifs: Neglected players in cancer?","volume":"10","author":"Uyar","year":"2014","journal-title":"Mol. Biosyst."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2804","DOI":"10.1523\/JNEUROSCI.08-08-02804.1988","article-title":"Synuclein: A neuron-specific protein localized to the nucleus and presynaptic nerve terminal","volume":"8","author":"Maroteaux","year":"1988","journal-title":"J. Neurosci."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1006\/exnr.2000.7615","article-title":"Differential expression and distribution of \u03b1-, \u03b2-, and \u03b3-synuclein in the developing human substantia nigra","volume":"168","author":"Galvin","year":"2001","journal-title":"Exp. Neurol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.neurobiolaging.2016.06.020","article-title":"Combinational losses of synucleins reveal their differential requirements for compensating age-dependent alterations in motor behavior and dopamine metabolism","volume":"46","author":"Peters","year":"2016","journal-title":"Neurobiol. Aging"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"14966","DOI":"10.1073\/pnas.0406283101","article-title":"Double-knockout mice for \u03b1- and \u03b2-Synucleins: Effect on synaptic functions","volume":"101","author":"Chandra","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1663","DOI":"10.1126\/science.1195227","article-title":"Alpha-synuclein promotes SNARE-complex assembly in vivo and in vitro","volume":"329","author":"Burre","year":"2010","journal-title":"Science"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"4673","DOI":"10.1093\/nar\/22.22.4673","article-title":"CLUSTAL W: Improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice","volume":"22","author":"Thompson","year":"1994","journal-title":"Nucleic Acids Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"W320","DOI":"10.1093\/nar\/gku316","article-title":"Deciphering key features in protein structures with the new ENDscript server","volume":"42","author":"Robert","year":"2014","journal-title":"Nucleic Acids Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1006\/exnr.1999.7228","article-title":"The expression of \u03b1-, \u03b2-, and \u03b3-synucleins in olfactory mucosa from patients with and without neurodegenerative diseases","volume":"160","author":"Duda","year":"1999","journal-title":"Exp. Neurol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/0014-5793(94)00395-5","article-title":"Identification of two distinct synucleins from human brain","volume":"345","author":"Jakes","year":"1994","journal-title":"FEBS Lett."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2845","DOI":"10.1097\/00001756-200109170-00018","article-title":"Expression of \u03b2-Synuclein in normal human astrocytes","volume":"12","author":"Tanji","year":"2001","journal-title":"Neuroreport"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"628","DOI":"10.4049\/jimmunol.170.1.628","article-title":"Autoimmune encephalomyelitis and uveitis induced by T Cell immunity to self \u03b2-Synuclein","volume":"170","author":"Mor","year":"2003","journal-title":"J. Immunol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1093\/jn\/138.5.841","article-title":"\u03b3-Synuclein is an adipocyte-neuron gene coordinately expressed with leptin and increased in human obesity","volume":"138","author":"Oort","year":"2008","journal-title":"J. Nutr."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"3419","DOI":"10.1096\/fj.07-8379rev","article-title":"\u03b3-Synuclein and the progression of cancer","volume":"21","author":"Ahmad","year":"2007","journal-title":"FASEB J."},{"key":"ref_20","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_21","doi-asserted-by":"crossref","first-page":"11970","DOI":"10.1074\/jbc.M109541200","article-title":"Biophysical properties of the synucleins and their propensities to fibrillate: Inhibition of \u03b1-synuclein assembly by \u03b2- and \u03b3-synucleins","volume":"277","author":"Uversky","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"708","DOI":"10.1016\/j.jmb.2007.07.009","article-title":"Structural characterization of the intrinsically unfolded protein \u03b2-Synuclein, a natural negative regulator of \u03b1-synuclein aggregation","volume":"372","author":"Bertoncini","year":"2007","journal-title":"J. Mol. Biol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"3830","DOI":"10.1021\/acs.biochem.8b00343","article-title":"Comparative analysis of the conformation, aggregation, interaction, and fibril morphologies of human \u03b1-, \u03b2-, and \u03b3-synuclein proteins","volume":"57","author":"Jain","year":"2018","journal-title":"Biochemistry"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1046\/j.0014-2956.2001.02633.x","article-title":"A Raman optical activity study of rheomorphism in caseins, synucleins and tau: New insight into the structure and behaviour of natively unfolded proteins","volume":"269","author":"Syme","year":"2002","journal-title":"Eur. J. Biochem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"6371","DOI":"10.1074\/jbc.M112.403311","article-title":"In vivo cross-linking reveals principally oligomeric forms of \u03b1-synuclein and \u03b2-Synuclein in neurons and non-neural cells","volume":"288","author":"Dettmer","year":"2013","journal-title":"J. Biol. Chem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/srep36010","article-title":"\u03b2-Synuclein suppresses both the initiation and amplification steps of \u03b1-synuclein aggregation via competitive binding to surfaces","volume":"6","author":"Brown","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"23622","DOI":"10.1074\/jbc.M313784200","article-title":"\u03b2-Synuclein regulates Akt activity in neuronal cells: A possible mechanism for neuroprotection in Parkinson\u2019s disease","volume":"279","author":"Hashimoto","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/srep15164","article-title":"Unveiling transient protein-protein interactions that modulate inhibition of alpha-synuclein aggregation by beta-synuclein, a pre-synaptic protein that co-localizes with alpha-synuclein","volume":"5","author":"Janowska","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"5989","DOI":"10.1021\/acs.biochem.8b00780","article-title":"Vibrational circular dichroism sheds new light on the competitive effects of crowding and \u03b2-Synuclein on the fibrillation process of \u03b1-synuclein","volume":"57","author":"Baatsen","year":"2018","journal-title":"Biochemistry"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1862","DOI":"10.1111\/j.1742-4658.2007.05733.x","article-title":"Dynamics of \u03b1-synuclein aggregation and inhibition of pore-like oligomer development by \u03b2-Synuclein","volume":"274","author":"Tsigelny","year":"2007","journal-title":"FEBS J."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Leitao, A., Bhumkar, A., Hunter, D., Gambin, Y., and Sierecki, E. (2018). Unveiling a selective mechanism for the inhibition of \u03b1-synuclein aggregation by \u03b2-Synuclein. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19020334"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1007\/s00018-014-1754-5","article-title":"Small heat-shock proteins: Important players in regulating cellular proteostasis","volume":"72","author":"Treweek","year":"2015","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1007\/s12192-020-01098-w","article-title":"The multifaceted nature of \u03b1B-crystallin","volume":"25","author":"Hayashi","year":"2020","journal-title":"Cell Stress Chaperones"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1038\/s41594-020-0384-x","article-title":"A short motif in the N-terminal region of \u03b1-synuclein is critical for both aggregation and function","volume":"27","author":"Doherty","year":"2020","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"995","DOI":"10.1096\/fj.201700675R","article-title":"Levels of \u03b1- and \u03b2-Synuclein regulate cellular susceptibility to toxicity from \u03b1-synuclein oligomers","volume":"32","author":"Angelova","year":"2018","journal-title":"FASEB J."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"869","DOI":"10.1096\/fj.01-0995fje","article-title":"Preferential transformation of human neuronal cells by human adenoviruses and the origin of HEK 293 cells","volume":"16","author":"Shaw","year":"2002","journal-title":"FASEB J."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"3002","DOI":"10.1093\/hmg\/ddl242","article-title":"\u03b2-Synuclein modulates \u03b1-synuclein neurotoxicity by reducing \u03b1-synuclein protein expression","volume":"15","author":"Fan","year":"2006","journal-title":"Hum. Mol. Genet."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/S0304-3940(00)01701-8","article-title":"Proteasomal function is impaired in substantia nigra in Parkinson\u2019s disease","volume":"297","author":"McNaught","year":"2001","journal-title":"Neurosci. Lett."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"7562","DOI":"10.1074\/jbc.M412887200","article-title":"\u03b2-Synuclein reduces proteasomal inhibition by \u03b1-synuclein but not \u03b3-synuclein","volume":"280","author":"Snyder","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_40","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 \u03b2-Synuclein-derived peptides","volume":"19","author":"Windisch","year":"2002","journal-title":"J. Mol. Neurosci."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1016\/S0896-6273(01)00462-7","article-title":"\u03b2-Synuclein inhibits \u03b1-synuclein aggregation: A possible role as an anti-Parkinsonian factor","volume":"32","author":"Hashimoto","year":"2001","journal-title":"Neuron"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1713","DOI":"10.1038\/sj.gt.3302349","article-title":"An antiaggregation gene therapy strategy for Lewy body disease utilizing \u03b2-Synuclein lentivirus in a transgenic model","volume":"11","author":"Hashimoto","year":"2004","journal-title":"Gene Ther."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Shaltiel-Karyo, R., Frenkel-Pinter, M., Egoz-Matia, N., Frydman-Marom, A., Shalev, D.E., Segal, D., and Gazit, E. (2010). Inhibiting \u03b1-synuclein oligomerization by stable cell-penetrating \u03b2-Synuclein fragments recovers phenotype of Parkinson\u2019s disease model flies. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0013863"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1016\/j.febslet.2004.08.075","article-title":"\u03b2-Synuclein exhibits chaperone activity more efficiently than \u03b1-synuclein","volume":"576","author":"Lee","year":"2004","journal-title":"FEBS Lett."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1042\/bj3230539","article-title":"Binding of A\u03b2 to \u03b1- and \u03b2-Synucleins: Identification of segments in \u03b1-synuclein\/NAC precursor that bind A\u03b2 and NAC","volume":"323","author":"Jensen","year":"1997","journal-title":"Biochem. J."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1167","DOI":"10.1016\/j.jmb.2004.05.054","article-title":"Interaction of the molecular chaperone \u03b1B-crystallin with \u03b1-synuclein: Effects on amyloid fibril formation and chaperone activity","volume":"340","author":"Rekas","year":"2004","journal-title":"J. Mol. Biol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"9110","DOI":"10.1073\/pnas.171300598","article-title":"\u03b1-synuclein occurs in lipid-rich high molecular weight complexes, binds fatty acids, and shows homology to the fatty acid-binding proteins","volume":"98","author":"Sharon","year":"2001","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1829","DOI":"10.1074\/jbc.M112.418871","article-title":"Monomeric synucleins generate membrane curvature","volume":"288","author":"Westphal","year":"2013","journal-title":"J. Biol. Chem."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"49874","DOI":"10.1074\/jbc.M309127200","article-title":"Altered fatty acid composition of dopaminergic neurons expressing \u03b1-synuclein and human brains with \u03b1-synucleinopathies","volume":"278","author":"Sharon","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1006\/exnr.2000.7527","article-title":"In situ and in vitro study of colocalization and segregation of \u03b1-synuclein, ubiquitin, and lipids in Lewy bodies","volume":"166","author":"Gai","year":"2000","journal-title":"Exp. Neurol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1111\/j.1471-4159.2008.05776.x","article-title":"\u03b2-Synuclein occurs in vivo in lipid-associated oligomers and forms hetero-oligomers with \u03b1-synuclein","volume":"108","author":"Israeli","year":"2009","journal-title":"J. Neurochem."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/j.brainres.2007.07.027","article-title":"An investigation into the lipid-binding properties of \u03b1-, \u03b2- and \u03b3-synucleins in human brain and cerebrospinal fluid","volume":"1170","author":"Salem","year":"2007","journal-title":"Brain Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"528","DOI":"10.1016\/j.jmb.2012.08.008","article-title":"Quantifying interactions of \u03b2-Synuclein and \u03b3-synuclein with model membranes","volume":"423","author":"Ducas","year":"2012","journal-title":"J. Mol. Biol."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Carnazza, K.E., Komer, L., Pineda, A., Na, Y., Ramlall, T., Buchman, V.L., Eliezer, D., Sharma, M., and Burre, J. (2020). Beta- and gamma-synucleins modulate synaptic vesicle-binding of alpha-synuclein. bioRxiv.","DOI":"10.1101\/2020.11.19.390419"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1110\/ps.073181508","article-title":"Molecular determinants of the aggregation behavior of \u03b1- and \u03b2-Synuclein","volume":"17","author":"Rivers","year":"2008","journal-title":"Protein Sci."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1162","DOI":"10.1110\/ps.051803606","article-title":"Secondary structure and dynamics of micelle bound \u03b2- and \u03b3-synuclein","volume":"15","author":"Sung","year":"2006","journal-title":"Protein Sci."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"32486","DOI":"10.1074\/jbc.M110.139576","article-title":"Membrane curvature induction and tubulation are common features of synucleins and apolipoproteins","volume":"285","author":"Varkey","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1038\/s41586-021-03819-2","article-title":"Highly accurate protein structure prediction with AlphaFold","volume":"596","author":"Jumper","year":"2021","journal-title":"Nature"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"3696","DOI":"10.1021\/bi020604a","article-title":"\u03b2-Synuclein inhibits formation of \u03b1-synuclein protofibrils: A possible therapeutic strategy against Parkinson\u2019s disease","volume":"42","author":"Park","year":"2003","journal-title":"Biochemistry"},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Hayashi, J., Ton, J., Negi, S., Stephens, D.E., Pountney, D.L., Preiss, T., and Carver, J.A. (2021). The effect of oxidized dopamine on the structure and molecular chaperone function of the small heat-shock proteins, \u03b1B-crystallin and Hsp27. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22073700"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1214","DOI":"10.1038\/nm1314","article-title":"Dopamine covalently modifies and functionally inactivates parkin","volume":"11","author":"LaVoie","year":"2005","journal-title":"Nat. Med."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1255","DOI":"10.1126\/science.aam9080","article-title":"Dopamine oxidation mediates mitochondrial and lysosomal dysfunction in Parkinson\u2019s disease","volume":"357","author":"Burbulla","year":"2017","journal-title":"Science"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"101375","DOI":"10.1016\/j.jbc.2021.101375","article-title":"\u03b2-Synuclein potentiates synaptic vesicle dopamine uptake and rescues dopaminergic neurons from MPTP-induced death in the absence of other synucleins","volume":"297","author":"Ninkina","year":"2021","journal-title":"J. Biol. Chem."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1021\/ic502407w","article-title":"Differences in the binding of copper(I) to \u03b1- and \u03b2-Synuclein","volume":"54","author":"Valensin","year":"2015","journal-title":"Inorg. Chem."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1016\/S0140-6736(87)90827-0","article-title":"Raised cerebrospinal-fluid copper concentration in Parkinson\u2019s disease","volume":"330","author":"Pall","year":"1987","journal-title":"Lancet"},{"key":"ref_66","first-page":"239","article-title":"Occupational exposure to manganese, copper, lead, iron, mercury and zinc and the risk of Parkinson\u2019s disease","volume":"20","author":"Gorell","year":"1999","journal-title":"Neurotoxicology"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/S0022-510X(98)00092-6","article-title":"Copper, iron and zinc in Alzheimer\u2019s disease senile plaques","volume":"158","author":"Lovell","year":"1998","journal-title":"J. Neurol. Sci."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"2384","DOI":"10.1096\/fj.09-130039","article-title":"Unique copper-induced oligomers mediate alpha-synuclein toxicity","volume":"23","author":"Wright","year":"2009","journal-title":"FASEB J."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"11801","DOI":"10.1021\/ja803494v","article-title":"Site-specific interactions of Cu(II) with \u03b1 and \u03b2-Synuclein: Bridging the molecular gap between metal binding and aggregation","volume":"130","author":"Binolfi","year":"2008","journal-title":"J. Am. Chem. Soc."},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Davies, P., Moualla, D., and Brown, D.R. (2011). Alpha-synuclein is a cellular ferrireductase. PLoS ONE, 6.","DOI":"10.1371\/annotation\/900a5247-7d03-4686-a544-5f7f64c0aac5"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"9096","DOI":"10.1021\/bi048778a","article-title":"Forcing nonamyloidogenic \u03b2-Synuclein to fibrillate","volume":"44","author":"Yamin","year":"2005","journal-title":"Biochemistry"},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"McHugh, P.C., Wright, J.A., and Brown, D.R. (2011). Transcriptional regulation of the beta-synuclein 5\u2032-promoter metal response element by metal transcription factor-1. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0017354"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"37330","DOI":"10.1074\/jbc.M306083200","article-title":"\u03b2-Synuclein displays an antiapoptotic p53-dependent phenotype and protects neurons from 6-hydroxydopamine-induced caspase 3 activation: Cross-talk with \u03b1-synuclein and implication for Parkinson\u2019s disease","volume":"278","author":"Masliah","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"796","DOI":"10.1177\/0963689718755706","article-title":"Age-related beta-synuclein alters the p53\/Mdm2 pathway and induces the apoptosis of brain microvascular endothelial cells in vitro","volume":"27","author":"Brockhaus","year":"2018","journal-title":"Cell Transplant."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"a033993","DOI":"10.1101\/cshperspect.a033993","article-title":"The autophagy lysosomal pathway and neurodegeneration","volume":"12","author":"Finkbeiner","year":"2020","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.brainres.2017.12.026","article-title":"Accumulation of beta-synuclein in cortical neurons is associated with autophagy attenuation in the brains of dementia with Lewy body patients","volume":"1681","author":"Evans","year":"2018","journal-title":"Brain Res."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"94","DOI":"10.3389\/fnmol.2018.00094","article-title":"Sumoylation protects against \u03b2-Synuclein toxicity in yeast","volume":"11","author":"Popova","year":"2018","journal-title":"Front. Mol. Neurosci."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"16368","DOI":"10.1074\/jbc.M117.780528","article-title":"A pH-dependent switch promotes \u03b2-Synuclein fibril formation via glutamate residues","volume":"292","author":"Moriarty","year":"2017","journal-title":"J. Biol. Chem."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"13450","DOI":"10.1073\/pnas.96.23.13450","article-title":"Axon pathology in Parkinson\u2019s disease and Lewy body dementia hippocampus contains alpha -, beta -, and gamma -synuclein","volume":"96","author":"Galvin","year":"1999","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"3126","DOI":"10.1074\/mcp.M116.059915","article-title":"Alpha-, beta-, and gamma-synuclein quantification in cerebrospinal fluid by multiple reaction monitoring reveals increased concentrations in Alzheimer\u2019s and Creutzfeldt-Jakob disease but no alteration in synucleinopathies","volume":"15","author":"Oeckl","year":"2016","journal-title":"Mol. Cell. Proteom."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1783","DOI":"10.1097\/00001756-200310060-00005","article-title":"Reciprocal accumulation of \u03b2-Synuclein in \u03b1-synuclein lesions in multiple system atrophy","volume":"14","author":"Mori","year":"2003","journal-title":"Neuroreport"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/j.neuint.2012.12.001","article-title":"Alzheimer disease periventricular white matter lesions exhibit specific proteomic profile alterations","volume":"62","author":"Maarouf","year":"2013","journal-title":"Neurochem. Int."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1016\/S0002-9440(10)64548-8","article-title":"Neurodegeneration with brain iron accumulation, type 1 is characterized by \u03b1-, \u03b2-, and \u03b3-synuclein neuropathology","volume":"157","author":"Galvin","year":"2000","journal-title":"Am. J. Pathol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"6734","DOI":"10.1007\/s12035-017-0846-2","article-title":"Pla2g6 deficiency in zebrafish leads to dopaminergic cell death, axonal degeneration, increased \u03b2-Synuclein expression, and defects in brain functions and pathways","volume":"55","author":"Azcona","year":"2018","journal-title":"Mol. Neurobiol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1731","DOI":"10.1126\/science.1062960","article-title":"The influence of the proinflammatory cytokine, osteopontin, on autoimmue demyelinating desease","volume":"294","author":"Chabas","year":"2001","journal-title":"Science"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1097\/00001756-200303240-00004","article-title":"Neuronal accumulation of \u03b1- and \u03b2-Synucleins in the brain of a GM2 gangliosidosis mouse model","volume":"14","author":"Suzuki","year":"2003","journal-title":"Neuroreport"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1007\/s00401-007-0264-z","article-title":"Neuronal and glial accumulation of \u03b1- and \u03b2-Synucleins in human lipidoses","volume":"114","author":"Suzuki","year":"2007","journal-title":"Acta Neuropathol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"4503871","DOI":"10.1155\/2018\/4503871","article-title":"Significant changes in plasma alpha-synuclein and beta-synuclein levels in male children with autism spectrum disorder","volume":"2018","author":"Sriwimol","year":"2018","journal-title":"Biomed Res. Int."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1007\/s00401-003-0718-x","article-title":"Expression of \u03b1-, \u03b2-, and \u03b3-synuclein in glial tumor and medulloblastomas","volume":"106","author":"Fung","year":"2003","journal-title":"Acta Neuropathol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/S0006-8993(01)02772-X","article-title":"Altered expression of the synuclein family mRNA in Lewy body and Alzheimer\u2019s disease","volume":"914","author":"Rockenstein","year":"2001","journal-title":"Brain Res."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1089\/gtmb.2010.0050","article-title":"Alpha-and beta-synucleins mRNA expression in lymphocytes of schizophrenia patients","volume":"14","author":"Kheirollahi","year":"2010","journal-title":"Genet. Test. Mol. Biomarkers"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1016\/j.neulet.2007.05.021","article-title":"Beta-synuclein gene variants and Parkinson\u2019s disease: A preliminary case-control study","volume":"420","author":"Brighina","year":"2007","journal-title":"Neurosci. Lett."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"970","DOI":"10.1001\/archneurol.2010.177","article-title":"Association of \u03b1-, \u03b2-, and \u03b3-synuclein with diffuse lewy body disease","volume":"67","author":"Nishioka","year":"2010","journal-title":"Arch. Neurol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1002\/ana.23905","article-title":"\u03b2-Synuclein aggregates and induces neurodegeneration in dopaminergic neurons","volume":"74","author":"Taschenberger","year":"2013","journal-title":"Ann. Neurol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1093\/hmg\/ddv470","article-title":"Yeast reveals similar molecular mechanisms underlying alpha- and beta-synuclein toxicity","volume":"25","author":"Tenreiro","year":"2016","journal-title":"Hum. Mol. Genet."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.jneuroim.2008.12.009","article-title":"Autoimmune spread to myelin is associated with experimental autoimmune encephalomyelitis induced by a neuronal protein, \u03b2-Synuclein","volume":"208","author":"Ronen","year":"2009","journal-title":"J. Neuroimmunol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1038\/s41586-019-0964-2","article-title":"\u03b2-Synuclein-reactive T cells induce autoimmune CNS grey matter degeneration","volume":"566","author":"Lodygin","year":"2019","journal-title":"Nature"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1212\/01.WNL.0000139870.14385.3C","article-title":"\u03b2-Synuclein gene alterations in dementia with Lewy bodies","volume":"63","author":"Ohtake","year":"2004","journal-title":"Neurology"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1038\/ncomms1101","article-title":"A \u03b2-Synuclein mutation linked to dementia produces neurodegeneration when expressed in mouse brain","volume":"1","author":"Fujita","year":"2010","journal-title":"Nat. Commun."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1186\/s13041-018-0378-3","article-title":"Immature-like molecular expression patterns in the hippocampus of a mouse model of dementia with Lewy body-linked mutant \u03b2-Synuclein","volume":"11","author":"Hagihara","year":"2018","journal-title":"Mol. Brain"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1002\/pro.2798","article-title":"The loss of inhibitory C-terminal conformations in disease associated P123H \u03b2-Synuclein","volume":"25","author":"Janowska","year":"2016","journal-title":"Protein Sci."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"28904","DOI":"10.1074\/jbc.M703711200","article-title":"Enhanced lysosomal pathology caused by \u03b2-Synuclein mutants linked to dementia with Lewy bodies","volume":"282","author":"Wei","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"1080","DOI":"10.1046\/j.1471-4159.2001.00655.x","article-title":"Cytosolic O-glycosylation is abundant in nerve terminals","volume":"79","author":"Cole","year":"2001","journal-title":"J. Neurochem."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"32619","DOI":"10.1074\/jbc.M605421200","article-title":"Proteomic identification of novel substrates of a protein isoaspartyl methyltransferase repair enzyme","volume":"281","author":"Vigneswara","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_105","doi-asserted-by":"crossref","unstructured":"Vigneswara, V., Cass, S., Wayne, D., Bolt, E.L., Ray, D.E., and Carter, W.G. (2013). Molecular ageing of alpha- and beta-synucleins: Protein damage and repair mechanisms. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0061442"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"2807","DOI":"10.1074\/jbc.M109.081950","article-title":"Phosphorylation of synucleins by members of the Polo-like kinase family","volume":"285","author":"Mbefo","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"26515","DOI":"10.1074\/jbc.M003542200","article-title":"Synucleins are a novel class of substrates for G protein-coupled receptor kinases","volume":"275","author":"Pronin","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"1001","DOI":"10.1016\/j.jmb.2004.02.014","article-title":"Structural determinants of PLD2 inhibition by \u03b1-synuclein","volume":"337","author":"Payton","year":"2004","journal-title":"J. Mol. Biol."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"1057","DOI":"10.1111\/j.1432-1033.1993.tb18337.x","article-title":"A new brain-specific 14-kDa protein is a phosphoprotein","volume":"217","author":"Shigeo","year":"1993","journal-title":"Eur. J. Biochem."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"6667","DOI":"10.1021\/bi2001938","article-title":"Defining the substrate specificity determinants recognized by the active site of C-terminal Src kinase-homologous kinase (CHK) and identification of \u03b2-Synuclein as a potential CHK physiological substrate","volume":"50","author":"Ia","year":"2011","journal-title":"Biochemistry"},{"key":"ref_111","first-page":"55361","article-title":"Recombinant \u03b1-, \u03b2- and \u03b3-synucleins stimulate protein phosphatase 2a catalytic subunit activity in cell free assays","volume":"2017","author":"Lek","year":"2017","journal-title":"J. Vis. Exp."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"D535","DOI":"10.1093\/nar\/gkj109","article-title":"BioGRID: A general repository for interaction datasets","volume":"34","author":"Stark","year":"2006","journal-title":"Nucleic Acids Res."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1038\/nmeth.3179","article-title":"Directed evolution of APEX2 for electron microscopy and proximity labeling","volume":"12","author":"Lam","year":"2015","journal-title":"Nat. Methods"}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/12\/1\/142\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T14:02:21Z","timestamp":1760364141000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/12\/1\/142"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1,16]]},"references-count":113,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2022,1]]}},"alternative-id":["biom12010142"],"URL":"https:\/\/doi.org\/10.3390\/biom12010142","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,1,16]]}}}