{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T03:06:13Z","timestamp":1790996773066,"version":"4.1.0"},"reference-count":43,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2014,11,18]],"date-time":"2014-11-18T00:00:00Z","timestamp":1416268800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Department of Science and Technology, Government of India","award":["SR\/SO\/HS 0026\/2012"],"award-info":[{"award-number":["SR\/SO\/HS 0026\/2012"]}]},{"name":"National Health and Medical Research Council of Australia"},{"name":"Department of Biotechnology, Government of India"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Neurochemistry"],"published-print":{"date-parts":[[2014,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    This study has shown that purified recombinant human \u03b1\u2010synuclein (20\u00a0\u03bcM) causes membrane depolarization and loss of phosphorylation capacity of isolated purified rat brain mitochondria by activating permeability transition pore complex. In intact SHSY5Y (human neuroblastoma cell line) cells, lactacystin (5\u00a0\u03bcM), a proteasomal inhibitor, causes an accumulation of \u03b1\u2010synuclein with concomitant mitochondrial dysfunction and cell death. The effects of lactacystin on intact SHSY5Y cells are, however, prevented by knocking down \u03b1\u2010synuclein expression by specific siRNA. Furthermore, in wild\u2010type (non\u2010transfected) SHSY5Y cells, the effects of lactacystin on mitochondrial function and cell viability are also prevented by cyclosporin A (1\u00a0\u03bcM) which blocks the activity of the mitochondrial permeability transition pore. Likewise, in wild\u2010type SHSY5Y cells, typical mitochondrial poison like antimycin A (50\u00a0nM) produces loss of cell viability comparable to that of lactacystin (5\u00a0\u03bcM). These data, in combination with those from isolated brain mitochondria, strongly suggest that intracellularly accumulated \u03b1\u2010synuclein can interact with mitochondria in intact SHSY5Y cells causing dysfunction of the organelle which drives the cell death under our experimental conditions. The results have clear implications in the pathogenesis of sporadic Parkinson's disease.\n                    <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                      <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc12966-fig-0009-m.png\">\n                        <jats:alt-text>image<\/jats:alt-text>\n                      <\/jats:graphic>\n                    <\/jats:boxed-text>\n                  <\/jats:p>\n                  <jats:p>\u03b1\u2010Synuclein is shown to cause mitochondrial impairment through interaction with permeability transition pore complex in isolated preparations. Intracellular accumulation of \u03b1\u2010synuclein in SHSY5Y cells following proteasomal inhibition leads to mitochondrial impairment and cell death which could be prevented by knocking down \u03b1\u2010synuclein gene. The results link mitochondrial dysfunction and \u03b1\u2010synuclein accumulation, two key pathogenic mechanisms of Parkinson's disease, in a common damage pathway.<\/jats:p>","DOI":"10.1111\/jnc.12966","type":"journal-article","created":{"date-parts":[[2014,10,15]],"date-time":"2014-10-15T13:55:43Z","timestamp":1413381343000},"page":"868-877","source":"Crossref","is-referenced-by-count":48,"title":["\u03b1\u2010synuclein\u2010induced mitochondrial dysfunction in isolated preparation and intact cells: Implications in the pathogenesis of Parkinson's disease"],"prefix":"10.1111","volume":"131","author":[{"given":"Aritri","family":"Bir","sequence":"first","affiliation":[{"name":"Department of Biochemistry Institute of Post Graduate Medical Education and Research Kolkata India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oishimaya","family":"Sen","sequence":"additional","affiliation":[{"name":"Department of Biochemistry Institute of Post Graduate Medical Education and Research Kolkata India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shruti","family":"Anand","sequence":"additional","affiliation":[{"name":"Department of Biochemistry Institute of Post Graduate Medical Education and Research Kolkata India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vineet Kumar","family":"Khemka","sequence":"additional","affiliation":[{"name":"Department of Biochemistry Institute of Post Graduate Medical Education and Research Kolkata India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Priyanjalee","family":"Banerjee","sequence":"additional","affiliation":[{"name":"Department of Biochemistry Institute of Post Graduate Medical Education and Research Kolkata India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"Cappai","sequence":"additional","affiliation":[{"name":"Department of Pathology and Bio21 Molecular Science and Biotechnology Institute The University of Melbourne Parkville Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arghyadip","family":"Sahoo","sequence":"additional","affiliation":[{"name":"Department of Biochemistry Institute of Post Graduate Medical Education and Research Kolkata India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sasanka","family":"Chakrabarti","sequence":"additional","affiliation":[{"name":"Department of Biochemistry Institute of Post Graduate Medical Education and Research Kolkata India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,11,18]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2009.02.007"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2010.03.012"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1155\/2014\/878935"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0062277"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2004.10.010"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.48.33855"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00762735"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2202-11-41"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00441-004-0956-9"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)62854-6"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1186\/1750\u20101326\u20104\u20109"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2007.05.022"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1042\/bj3410233"},{"key":"e_1_2_7_15_1","first-page":"2015","article-title":"Mitochondrial import and accumulation of alpha\u2010synuclein impairs complex I in human dopaminergic neuronal cultures and Parkinson's disease brain","volume":"41","author":"Devi L.","year":"2008","journal-title":"J. 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