{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T18:00:48Z","timestamp":1787508048439,"version":"build-2736575974"},"reference-count":0,"publisher":"SAGE Publications","issue":"1","license":[{"start":{"date-parts":[[2012,1,1]],"date-time":"2012-01-01T00:00:00Z","timestamp":1325376000000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Parkinson\u2019s Disease"],"published-print":{"date-parts":[[2012,2,1]]},"abstract":"<jats:p>Parkinson's disease (PD) can include a progressive frontal lobe \u03b1-synucleinopathy with disability from cognitive decline and cortico-limbic dysregulation that may arise from bioenergetic impairments. We examined in PD frontal cortex regulation of mitochondrial biogenesis (mitobiogenesis) and its effects on Complex-I. We quantified expression of 33 nuclear genome (nDNA)-encoded and 7 mitochondrial genome (mtDNA)-encoded Complex-I genes, 6 Complex-I assembly factors and multiple mitobiogenesis genes. We related these findings to levels of Complex-I proteins and NADH-driven electron flow in mitochondria from these same specimens reported in earlier studies. We found widespread, decreased expression of nDNA Complex-I genes that correlated in some cases with mitochondrial Complex-I protein levels, and of ACAD9, a Complex-I assembly factor. mtDNA-transcribed Complex-I genes showed ~ constant expression within each PD sample but variable expression across PD samples that correlated with NRF1. Relationships among PGC-1\u03b1 and its downstream targets NRF1 and TFAM were very similar in PD and CTL and were related to mitochondrial NADH-driven electron flow. MicroRNA arrays revealed multiple miRNA's regulated &gt;2-fold predicted to interact with PGC-1\u03b1 or its upstream regulators. Exposure of cultured human neurons to NO, rotenone and TNF-alpha partially reproduced mitobiogenesis down-regulation. In PD frontal cortex mitobiogenesis signaling relationships are maintained but down-regulated, correlate with impaired mitochondrial NADH-driven electron flow and may arise from combinations of nitrosative\/oxidative stresses, inflammatory cytokines, altered levels of mitobiogenesis gene-interacting microRNA's, or other unknown mechanisms. Stimulation of mitobiogenesis in PD may inhibit rostral disease progression and appearance of secondary symptoms referable to frontal cortex.<\/jats:p>","DOI":"10.3233\/jpd-2012-11074","type":"journal-article","created":{"date-parts":[[2019,12,3]],"date-time":"2019-12-03T13:52:16Z","timestamp":1575381136000},"page":"67-76","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":49,"title":["Impaired Complex-I Mitochondrial Biogenesis in Parkinson Disease                     Frontal Cortex"],"prefix":"10.1177","volume":"2","author":[{"given":"Ravindar R.","family":"Thomas","sequence":"first","affiliation":[{"name":"Parkinson's Disease Research Center, Virginia Commonwealth University,\r                    Richmond, VA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paula M.","family":"Keeney","sequence":"additional","affiliation":[{"name":"Parkinson's Disease Research Center, Virginia Commonwealth University,\r                    Richmond, VA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James P.","family":"Bennett","sequence":"additional","affiliation":[{"name":"Parkinson's Disease Research Center, Virginia Commonwealth University,\r                    Richmond, VA, USA"},{"name":"Department of Neurology, Virginia Commonwealth University, Richmond, VA,\r                    USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2012,1,1]]},"container-title":["Journal of Parkinson\u2019s Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.3233\/JPD-2012-11074","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.3233\/JPD-2012-11074","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T04:48:01Z","timestamp":1777610881000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.3233\/JPD-2012-11074"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,1,1]]},"references-count":0,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2012,2,1]]}},"alternative-id":["10.3233\/JPD-2012-11074"],"URL":"https:\/\/doi.org\/10.3233\/jpd-2012-11074","relation":{"is-cited-by":[{"id-type":"doi","id":"10.3389\/fnins.2018.00342","asserted-by":"object"},{"id-type":"doi","id":"10.3389\/fgene.2019.00435","asserted-by":"object"}]},"ISSN":["1877-7171","1877-718X"],"issn-type":[{"value":"1877-7171","type":"print"},{"value":"1877-718X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,1,1]]}}}