{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T00:49:52Z","timestamp":1777942192476,"version":"3.51.4"},"reference-count":69,"publisher":"The Company of Biologists","issue":"3-4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2010,3,8]]},"abstract":"<jats:title>SUMMARY<\/jats:title>\n               <jats:p>\u03b1-Synuclein (\u03b1-syn) is a small lipid-binding protein involved in vesicle trafficking whose function is poorly characterized. It is of great interest to human biology and medicine because \u03b1-syn dysfunction is associated with several neurodegenerative disorders, including Parkinson\u2019s disease (PD). We previously created a yeast model of \u03b1-syn pathobiology, which established vesicle trafficking as a process that is particularly sensitive to \u03b1-syn expression. We also uncovered a core group of proteins with diverse activities related to \u03b1-syn toxicity that is conserved from yeast to mammalian neurons. Here, we report that a yeast strain expressing a somewhat higher level of \u03b1-syn also exhibits strong defects in mitochondrial function. Unlike our previous strain, genetic suppression of endoplasmic reticulum (ER)-to-Golgi trafficking alone does not suppress \u03b1-syn toxicity in this strain. In an effort to identify individual compounds that could simultaneously rescue these apparently disparate pathological effects of \u03b1-syn, we screened a library of 115,000 compounds. We identified a class of small molecules that reduced \u03b1-syn toxicity at micromolar concentrations in this higher toxicity strain. These compounds reduced the formation of \u03b1-syn foci, re-established ER-to-Golgi trafficking and ameliorated \u03b1-syn-mediated damage to mitochondria. They also corrected the toxicity of \u03b1-syn in nematode neurons and in primary rat neuronal midbrain cultures. Remarkably, the compounds also protected neurons against rotenone-induced toxicity, which has been used to model the mitochondrial defects associated with PD in humans. That single compounds are capable of rescuing the diverse toxicities of \u03b1-syn in yeast and neurons suggests that they are acting on deeply rooted biological processes that connect these toxicities and have been conserved for a billion years of eukaryotic evolution. Thus, it seems possible to develop novel therapeutic strategies to simultaneously target the multiple pathological features of PD.<\/jats:p>","DOI":"10.1242\/dmm.004267","type":"journal-article","created":{"date-parts":[[2009,12,29]],"date-time":"2009-12-29T01:55:41Z","timestamp":1262051741000},"page":"194-208","source":"Crossref","is-referenced-by-count":146,"title":["Compounds from an unbiased chemical screen reverse both ER-to-Golgi trafficking defects and mitochondrial dysfunction in Parkinson\u2019s disease models"],"prefix":"10.1242","volume":"3","author":[{"given":"Linhui Julie","family":"Su","sequence":"first","affiliation":[{"name":"Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA"},{"name":"Present address: Adnexus Therapeutics, A Bristol-Myers Squibb R&D Company, Waltham, MA 02453, USA"}]},{"given":"Pavan K.","family":"Auluck","sequence":"additional","affiliation":[{"name":"Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA"},{"name":"Department of Pathology, Massachusetts General Hospital, Boston, MA 02114, and Harvard Medical School, Boston, MA 02115, USA"}]},{"given":"Tiago Fleming","family":"Outeiro","sequence":"additional","affiliation":[{"name":"Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA"},{"name":"Present address: Cell and Molecular Neuroscience Unit, Instituto de Medicina Molecular and Instituto de Fisiologia, Faculdade de Medicina da Universidade de Lisboa, Lisbon, Portugal"}]},{"given":"Esti","family":"Yeger-Lotem","sequence":"additional","affiliation":[{"name":"Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA"},{"name":"Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02142, USA"},{"name":"Present address: Department of Clinical Biochemistry, Soroka Medical Center and the National Institute for Biotechnology in the Negev, Ben-Gurion University of the Negev, Beer-Sheva, 84105, Israel"}]},{"given":"Joshua A.","family":"Kritzer","sequence":"additional","affiliation":[{"name":"Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA"},{"name":"Present address: Department of Chemistry, Tufts University, Medford, MA 02155, USA"}]},{"given":"Daniel F.","family":"Tardiff","sequence":"additional","affiliation":[{"name":"Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA"}]},{"given":"Katherine E.","family":"Strathearn","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, IN 47907, USA"}]},{"given":"Fang","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, IN 47907, USA"}]},{"given":"Songsong","family":"Cao","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, University of Alabama, Tuscaloosa, AL 35487, USA"}]},{"given":"Shusei","family":"Hamamichi","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, University of Alabama, Tuscaloosa, AL 35487, USA"}]},{"given":"Kathryn J.","family":"Hill","sequence":"additional","affiliation":[{"name":"Diabetes Program, Garvan Institute of Medical Research, Sydney 2010, New South Wales, and School of Biotechnology and Biomolecular Sciences, Faculty of Science, University of New South Wales, Sydney 2052, New South Wales, Australia"}]},{"given":"Kim A.","family":"Caldwell","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, University of Alabama, Tuscaloosa, AL 35487, USA"}]},{"given":"George W.","family":"Bell","sequence":"additional","affiliation":[{"name":"Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA"}]},{"given":"Ernest","family":"Fraenkel","sequence":"additional","affiliation":[{"name":"Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02142, USA"}]},{"given":"Antony A.","family":"Cooper","sequence":"additional","affiliation":[{"name":"Diabetes Program, Garvan Institute of Medical Research, Sydney 2010, New South Wales, and School of Biotechnology and Biomolecular Sciences, Faculty of Science, University of New South Wales, Sydney 2052, New South Wales, Australia"}]},{"given":"Guy A.","family":"Caldwell","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, University of Alabama, Tuscaloosa, AL 35487, USA"}]},{"given":"J. Michael","family":"McCaffery","sequence":"additional","affiliation":[{"name":"Integrated Imaging Center, Department of Biology, Johns Hopkins University, Baltimore, MD 21218, USA"}]},{"given":"Jean-Christophe","family":"Rochet","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, IN 47907, USA"}]},{"given":"Susan","family":"Lindquist","sequence":"additional","affiliation":[{"name":"Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA"},{"name":"Howard Hughes Medical Institute, Cambridge, MA 02142, USA"}]}],"member":"237","reference":[{"key":"2021042500110562900_b1-0030194","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1016\/S0896-6273(00)80886-7","article-title":"Mice lacking alpha-synuclein display functional deficits in the nigrostriatal dopamine system","volume":"25","author":"Abeliovich","year":"2000","journal-title":"Neuron"},{"key":"2021042500110562900_b2-0030194","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1038\/nrn1868","article-title":"Expanding insights of mitochondrial dysfunction in Parkinson\u2019s disease","volume":"7","author":"Abou-Sleiman","year":"2006","journal-title":"Nat Rev Neurosci"},{"key":"2021042500110562900_b3-0030194","doi-asserted-by":"crossref","first-page":"1351","DOI":"10.1038\/nbt1297-1351","article-title":"Stress tolerance: the key to effective strains of industrial baker\u2019s yeast","volume":"15","author":"Attfield","year":"1997","journal-title":"Nat Biotechnol"},{"key":"2021042500110562900_b4-0030194","doi-asserted-by":"crossref","first-page":"986","DOI":"10.2741\/2119","article-title":"Mitochondrial toxins and neurodegenerative diseases","volume":"12","author":"Ayala","year":"2007","journal-title":"Front Biosci"},{"key":"2021042500110562900_b5-0030194","doi-asserted-by":"crossref","first-page":"D396","DOI":"10.1093\/nar\/gkn803","article-title":"The GOA database in 2009-an integrated Gene Ontology Annotation resource","volume":"37","author":"Barrell","year":"2009","journal-title":"Nucleic Acids Res"},{"key":"2021042500110562900_b6-0030194","doi-asserted-by":"crossref","first-page":"1301","DOI":"10.1038\/81834","article-title":"Chronic systemic pesticide exposure reproduces features of Parkinson\u2019s disease","volume":"3","author":"Betarbet","year":"2000","journal-title":"Nat Neurosci"},{"key":"2021042500110562900_b7-0030194","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":"Neurobio Aging"},{"key":"2021042500110562900_b8-0030194","doi-asserted-by":"crossref","first-page":"8797","DOI":"10.1523\/JNEUROSCI.22-20-08797.2002","article-title":"Synaptic vesicle depletion correlates with attenuated synaptic responses to prolonged repetitive stimulation in mice lacking alpha-synuclein","volume":"22","author":"Cabin","year":"2002","journal-title":"J Neurosci"},{"key":"2021042500110562900_b9-0030194","doi-asserted-by":"crossref","first-page":"3801","DOI":"10.1523\/JNEUROSCI.5157-04.2005","article-title":"Torsin-mediated protection from cellular stress in the dopaminergic neurons of Caenorhabditis elegans","volume":"25","author":"Cao","year":"2005","journal-title":"J Neurosci"},{"key":"2021042500110562900_b10-0030194","doi-asserted-by":"crossref","first-page":"30009","DOI":"10.1074\/jbc.M501308200","article-title":"Alpha-synuclein alters proteasome function, protein synthesis, and stationary phase viability","volume":"280","author":"Chen","year":"2005","journal-title":"J Biol Chem"},{"key":"2021042500110562900_b11-0030194","doi-asserted-by":"crossref","first-page":"6344","DOI":"10.1074\/jbc.M108414200","article-title":"Lipid droplet binding and oligomerization properties of the Parkinson\u2019s disease protein alpha-synuclein","volume":"277","author":"Cole","year":"2002","journal-title":"J Biol Chem"},{"key":"2021042500110562900_b12-0030194","doi-asserted-by":"crossref","first-page":"2076","DOI":"10.1016\/j.yexcr.2008.03.012","article-title":"Mitochondrial translocation of alpha-synuclein is promoted by intracellular acidification","volume":"10","author":"Cole","year":"2008","journal-title":"Exp Cell Res"},{"key":"2021042500110562900_b13-0030194","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1126\/science.1129462","article-title":"Alpha-synuclein blocks ER-Golgi traffic and Rab1 rescues neuron loss in Parkinson\u2019s models","volume":"313","author":"Cooper","year":"2006","journal-title":"Science"},{"key":"2021042500110562900_b14-0030194","doi-asserted-by":"crossref","first-page":"14524","DOI":"10.1073\/pnas.172514599","article-title":"Resistance of alpha-synuclein null mice to the parkinsonian neurotoxin MPTP","volume":"99","author":"Dauer","year":"2002","journal-title":"Proc Natl Acad Sci USA"},{"key":"2021042500110562900_b15-0030194","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/S0163-7827(97)00006-4","article-title":"Import of lipids into mitochondria","volume":"36","author":"Daum","year":"1997","journal-title":"Prog Lipid Res"},{"key":"2021042500110562900_b16-0030194","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/0165-1781(79)90006-4","article-title":"Chronic Parkinsonism secondary to intravenous injection of meperidine analogues","volume":"1","author":"Davis","year":"1979","journal-title":"Psychiatry Res"},{"key":"2021042500110562900_b17-0030194","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1038\/nature07534","article-title":"Mitofusin 2 tethers endoplasmic reticulum to mitochondria","volume":"456","author":"de Brito","year":"2008","journal-title":"Nature"},{"key":"2021042500110562900_b18-0030194","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1111\/j.1432-1033.1995.200_1.x","article-title":"Regulation of mitochondrial biogenesis in Saccharomyces cerevisiae. Intricate interplay between general and specific transcription factors in the promoter of the QCR8 gene","volume":"233","author":"De Winde","year":"1995","journal-title":"Euro J Biochemistry"},{"key":"2021042500110562900_b19-0030194","doi-asserted-by":"crossref","first-page":"9089","DOI":"10.1074\/jbc.M710012200","article-title":"Mitochondrial import and accumulation of alpha-synuclein impair complex I in human dopaminergic neuronal cultures and Parkinson disease brain","volume":"283","author":"Devi","year":"2008","journal-title":"J Biol Chem"},{"key":"2021042500110562900_b20-0030194","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1016\/j.neuro.2004.05.002","article-title":"Mice lacking alpha-synuclein have an attenuated loss of striatal dopamine following prolonged chronic MPTP administration","volume":"25","author":"Drolet","year":"2004","journal-title":"Neurotoxicol"},{"key":"2021042500110562900_b21-0030194","doi-asserted-by":"crossref","first-page":"11045","DOI":"10.1073\/pnas.0604547103","article-title":"Flanking sequences profoundly alter polyglutamine toxicity in yeast","volume":"103","author":"Duennwald","year":"2006","journal-title":"Proc Natl Acad Sci USA"},{"key":"2021042500110562900_b22-0030194","doi-asserted-by":"crossref","first-page":"10190","DOI":"10.1128\/MCB.25.22.10190-10201.2005","article-title":"Mitochondrial lipid abnormality and electron transport chain impairment in mice lacking alpha-synuclein","volume":"25","author":"Ellis","year":"2005","journal-title":"Mol Cell Biol"},{"key":"2021042500110562900_b23-0030194","doi-asserted-by":"crossref","first-page":"1847","DOI":"10.1093\/hmg\/10.17.1847","article-title":"alpha-Synuclein gene haplotypes are associated with Parkinson\u2019s disease","volume":"10","author":"Farrer","year":"2001","journal-title":"Human Mol Genet"},{"key":"2021042500110562900_b24-0030194","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1016\/S0076-6879(07)00425-9","article-title":"Detection of compounds that rescue rab1-synuclein toxicity","volume":"439","author":"Fleming","year":"2008","journal-title":"Methods Enzymol"},{"issue":"Suppl. 2","key":"2021042500110562900_b25-0030194","first-page":"1182","article-title":"Influence of neurotoxins and oxidative stress on the onset and progression of Parkinson\u2019s disease","volume":"247","author":"Foley","year":"2000","journal-title":"J. Neurol"},{"key":"2021042500110562900_b26-0030194","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 alpha-synuclein, ubiquitin, and lipids in Lewy bodies","volume":"166","author":"Gai","year":"2000","journal-title":"Exp Neurol"},{"key":"2021042500110562900_b27-0030194","doi-asserted-by":"crossref","first-page":"4241","DOI":"10.1091\/mbc.11.12.4241","article-title":"Genomic expression programs in the response of yeast cells to environmental changes","volume":"11","author":"Gasch","year":"2000","journal-title":"Mol Biol Cell"},{"key":"2021042500110562900_b28-0030194","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1073\/pnas.0710685105","article-title":"The Parkinson\u2019s disease protein alpha-synuclein disrupts cellular Rab homeostasis","volume":"105","author":"Gitler","year":"2008","journal-title":"Proc Natl Acad Sci USA"},{"key":"2021042500110562900_b29-0030194","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1038\/ng.300","article-title":"alpha-Synuclein is part of a diverse and highly conserved interaction network that includes PARK9 and manganese toxicity","volume":"3","author":"Gitler","year":"2009","journal-title":"Nat Genet"},{"key":"2021042500110562900_b30-0030194","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1016\/j.expneurol.2008.04.004","article-title":"Parkinson patient fibroblasts show increased alpha-synuclein expression","volume":"212","author":"Hoepken","year":"2008","journal-title":"Exp Neurol"},{"key":"2021042500110562900_b31-0030194","doi-asserted-by":"crossref","first-page":"D577","DOI":"10.1093\/nar\/gkm909","article-title":"Gene Ontology annotations at SGD: new data sources and annotation methods","volume":"36","author":"Hong","year":"2008","journal-title":"Nucleic Acids Res"},{"key":"2021042500110562900_b32-0030194","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1001\/archneurol.2008.555","article-title":"Alpha-synuclein gene rearrangements in dominantly inherited parkinsonism: frequency, phenotype, and mechanisms","volume":"66","author":"Ibanez","year":"2009","journal-title":"Arch Neurol"},{"key":"2021042500110562900_b33-0030194","doi-asserted-by":"crossref","first-page":"34328","DOI":"10.1074\/jbc.M004345200","article-title":"alpha-Synuclein membrane interactions and lipid specificity","volume":"275","author":"Jo","year":"2000","journal-title":"J Biol Chem"},{"key":"2021042500110562900_b34-0030194","volume-title":"Principles of Neural Science","author":"Kandel","year":"2000"},{"key":"2021042500110562900_b35-0030194","doi-asserted-by":"crossref","first-page":"1222","DOI":"10.1002\/ajmg.b.30758","article-title":"Genetic association between alpha-synuclein and idiopathic Parkinson\u2019s disease","volume":"147B","author":"Kay","year":"2008","journal-title":"Am. J. Med. Genet. B. Neuropsychiatr. Genet"},{"key":"2021042500110562900_b36-0030194","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1016\/j.nbd.2005.08.018","article-title":"Mice lacking alpha-synuclein are resistant to mitochondrial toxins","volume":"21","author":"Klivenyi","year":"2006","journal-title":"Neurobiol Dis"},{"key":"2021042500110562900_b37-0030194","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1126\/science.1175088","article-title":"An ER-mitochondria tethering complex revealed by a synthetic biology screen","volume":"325","author":"Kornmann","year":"2009","journal-title":"Science"},{"key":"2021042500110562900_b38-0030194","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1038\/nchembio.193","article-title":"Rapid selection of cyclic peptides that reduce alpha-synuclein toxicity in yeast and animal models","volume":"9","author":"Kritzer","year":"2009","journal-title":"Nat Chem Biol"},{"key":"2021042500110562900_b39-0030194","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":"Kruger","year":"1998","journal-title":"Nat Genet"},{"key":"2021042500110562900_b40-0030194","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1126\/science.6823561","article-title":"Chronic Parkinsonism in humans due to a product of meperidine-analog synthesis","volume":"219","author":"Langston","year":"1983","journal-title":"Science"},{"key":"2021042500110562900_b41-0030194","doi-asserted-by":"crossref","first-page":"2435","DOI":"10.1111\/j.1471-4159.2008.05333.x","article-title":"Mechanisms of DJ-1 neuroprotection in a cellular model of Parkinson\u2019s disease","volume":"105","author":"Liu","year":"2008","journal-title":"J Neurochem"},{"key":"2021042500110562900_b42-0030194","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1016\/j.freeradbiomed.2008.03.022","article-title":"Methionine sulfoxide reductase A protects dopaminergic cells from Parkinson\u2019s disease-related insults","volume":"45","author":"Liu","year":"2008","journal-title":"Free Radic Biol Med"},{"key":"2021042500110562900_b43-0030194","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1016\/S1097-2765(03)00285-5","article-title":"Retrograde signaling is regulated by the dynamic interaction between Rtg2p and Mks1p","volume":"12","author":"Liu","year":"2003","journal-title":"Mol Cell"},{"key":"2021042500110562900_b44-0030194","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/0378-1119(93)90681-R","article-title":"Fusion of GAL4-VP16 to a steroid-binding domain provides a tool for gratuitous induction of galactose-responsive genes in yeast","volume":"131","author":"Louvion","year":"1993","journal-title":"Gene"},{"key":"2021042500110562900_b45-0030194","doi-asserted-by":"crossref","first-page":"1707","DOI":"10.1242\/jcs.03443","article-title":"A cell biological perspective on mitochondrial dysfunction in Parkinson disease and other neurodegenerative diseases","volume":"120","author":"Mandemakers","year":"2007","journal-title":"J Cell Sci"},{"key":"2021042500110562900_b46-0030194","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1523\/JNEUROSCI.4308-05.2006","article-title":"Parkinson\u2019s disease alpha-synuclein transgenic mice develop neuronal mitochondrial degeneration and cell death","volume":"26","author":"Martin","year":"2006","journal-title":"J Neurosci"},{"key":"2021042500110562900_b47-0030194","first-page":"33","article-title":"Isolation of yeast mitochondria","volume":"313","author":"Meisinger","year":"2006","journal-title":"Methods Mol Biol"},{"key":"2021042500110562900_b48-0030194","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1016\/j.neuron.2009.01.033","article-title":"Interplay between cytosolic dopamine, calcium, and alpha-synuclein causes selective death of substantia nigra neurons","volume":"62","author":"Mosharov","year":"2009","journal-title":"Neuron"},{"key":"2021042500110562900_b49-0030194","doi-asserted-by":"crossref","first-page":"3214","DOI":"10.1523\/JNEUROSCI.20-09-03214.2000","article-title":"Synucleins are developmentally expressed, and alpha-synuclein regulates the size of the presynaptic vesicular pool in primary hippocampal neurons","volume":"20","author":"Murphy","year":"2000","journal-title":"J Neurosci"},{"key":"2021042500110562900_b50-0030194","doi-asserted-by":"crossref","first-page":"27230","DOI":"10.1074\/jbc.M212436200","article-title":"Effects of oxidative and nitrative challenges on alpha-synuclein fibrillogenesis involve distinct mechanisms of protein modifications","volume":"278","author":"Norris","year":"2003","journal-title":"J Biol Chem"},{"key":"2021042500110562900_b51-0030194","doi-asserted-by":"crossref","first-page":"658","DOI":"10.2353\/ajpath.2007.060359","article-title":"Pesticide exposure exacerbates alpha-synucleinopathy in an A53T transgenic mouse model","volume":"170","author":"Norris","year":"2007","journal-title":"Am J Pathol"},{"key":"2021042500110562900_b52-0030194","doi-asserted-by":"crossref","first-page":"1772","DOI":"10.1126\/science.1090439","article-title":"Yeast cells provide insight into alpha-synuclein biology and pathobiology","volume":"302","author":"Outeiro","year":"2003","journal-title":"Science"},{"key":"2021042500110562900_b53-0030194","doi-asserted-by":"crossref","first-page":"1272","DOI":"10.1007\/s00018-008-7589-1","article-title":"Mitochondrial association of alpha-synuclein causes oxidative stress","volume":"65","author":"Parihar","year":"2008","journal-title":"Cell Mol Life Sci"},{"key":"2021042500110562900_b54-0030194","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":"2021042500110562900_b55-0030194","doi-asserted-by":"crossref","first-page":"46915","DOI":"10.1074\/jbc.M405146200","article-title":"alpha-Synuclein is required for the fibrillar nature of ubiquitinated inclusions induced by proteasomal inhibition in primary neurons","volume":"279","author":"Rideout","year":"2004","journal-title":"J Biol Chem"},{"key":"2021042500110562900_b56-0030194","doi-asserted-by":"crossref","first-page":"3091","DOI":"10.1093\/nar\/18.10.3091","article-title":"A rapid and simple method for preparation of RNA from Saccharomyces cerevisiae","volume":"18","author":"Schmitt","year":"1990","journal-title":"Nucleic Acids Res"},{"key":"2021042500110562900_b57-0030194","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1002\/ana.21685","article-title":"SNCA variants are associated with increased risk for multiple system atrophy","volume":"65","author":"Scholz","year":"2009","journal-title":"Ann Neurol"},{"key":"2021042500110562900_b58-0030194","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1385\/JMN:28:2:161","article-title":"alpha-Synuclein budding yeast model: toxicity enhanced by impaired proteasome and oxidative stress","volume":"28","author":"Sharma","year":"2006","journal-title":"J Mol Neurosci"},{"key":"2021042500110562900_b59-0030194","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1006\/exnr.2002.8072","article-title":"Subcutaneous rotenone exposure causes highly selective dopaminergic degeneration and alpha-synuclein aggregation","volume":"179","author":"Sherer","year":"2003","journal-title":"Experimental Neurol"},{"key":"2021042500110562900_b60-0030194","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1126\/science.1090278","article-title":"alpha-Synuclein locus triplication causes Parkinson\u2019s disease","volume":"302","author":"Singleton","year":"2003","journal-title":"Science"},{"key":"2021042500110562900_b61-0030194","doi-asserted-by":"crossref","first-page":"3801","DOI":"10.1093\/hmg\/ddi396","article-title":"Endoplasmic reticulum stress and mitochondrial cell death pathways mediate A53T mutant alpha-synuclein-induced toxicity","volume":"14","author":"Smith","year":"2005","journal-title":"Human Mol Genet"},{"key":"2021042500110562900_b62-0030194","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1016\/S0014-4886(03)00342-X","article-title":"Enhanced substantia nigra mitochondrial pathology in human alpha-synuclein transgenic mice after treatment with MPTP","volume":"186","author":"Song","year":"2004","journal-title":"Exp Neurol"},{"key":"2021042500110562900_b63-0030194","doi-asserted-by":"crossref","first-page":"1093","DOI":"10.1091\/mbc.e07-08-0827","article-title":"Alpha-synuclein-induced aggregation of cytoplasmic vesicles in Saccharomyces cerevisiae","volume":"19","author":"Soper","year":"2008","journal-title":"Mol Biol Cell"},{"key":"2021042500110562900_b64-0030194","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1038\/42166","article-title":"Alpha-synuclein in Lewy bodies","volume":"388","author":"Spillantini","year":"1997","journal-title":"Nature"},{"key":"2021042500110562900_b65-0030194","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/S0304-3940(98)00504-7","article-title":"Filamentous alpha-synuclein inclusions link multiple system atrophy with Parkinson\u2019s disease and dementia with Lewy bodies","volume":"251","author":"Spillantini","year":"1998","journal-title":"Neurosci Lett"},{"key":"2021042500110562900_b66-0030194","doi-asserted-by":"crossref","first-page":"2377","DOI":"10.1093\/hmg\/ddm083","article-title":"Mono- and double-mutant mouse models of Parkinson\u2019s disease display severe mitochondrial damage","volume":"16","author":"Stichel","year":"2007","journal-title":"Human Mol Genet"},{"key":"2021042500110562900_b67-0030194","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/j.expneurol.2009.03.019","article-title":"Mitochondrial dynamics in Parkinson\u2019s disease","volume":"2","author":"Van Laar","year":"2009","journal-title":"Exp Neurol"},{"key":"2021042500110562900_b68-0030194","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1016\/S0092-8674(00)80450-X","article-title":"Bcl-xL regulates the membrane potential and volume homeostasis of mitochondria","volume":"91","author":"Vander Heiden","year":"1997","journal-title":"Cell"},{"key":"2021042500110562900_b69-0030194","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1038\/ng.337","article-title":"Bridging high-throughput genetic and transcriptional data reveals cellular responses to alpha-synuclein toxicity","volume":"41","author":"Yeger-Lotem","year":"2009","journal-title":"Nat Genet"}],"container-title":["Disease Models &amp; Mechanisms"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/journals.biologists.com\/dmm\/article-pdf\/3\/3-4\/194\/1618067\/194.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/journals.biologists.com\/dmm\/article-pdf\/3\/3-4\/194\/1618067\/194.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,4,25]],"date-time":"2021-04-25T00:12:02Z","timestamp":1619309522000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.biologists.com\/dmm\/article\/3\/3-4\/194\/2362\/Compounds-from-an-unbiased-chemical-screen-reverse"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,3,8]]},"references-count":69,"journal-issue":{"issue":"3-4","published-print":{"date-parts":[[2010,3,8]]}},"URL":"https:\/\/doi.org\/10.1242\/dmm.004267","relation":{},"ISSN":["1754-8411","1754-8403"],"issn-type":[{"value":"1754-8411","type":"electronic"},{"value":"1754-8403","type":"print"}],"subject":[],"published":{"date-parts":[[2010,3,8]]}}}