{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T12:18:44Z","timestamp":1791980324838,"version":"4.4.0"},"reference-count":61,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2014,1,7]],"date-time":"2014-01-07T00:00:00Z","timestamp":1389052800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["5P01 (AG14930)"],"award-info":[{"award-number":["5P01 (AG14930)"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2014,4]]},"abstract":"<jats:p>\n                    The peroxisome proliferator\u2010activated receptor \u03b3 coactivator 1\u2010\u03b1 (PGC\u20101\u03b1) interacts with various transcription factors involved in energy metabolism and in the regulation of mitochondrial biogenesis. PGC\u20101\u03b1 mRNA levels are reduced in a number of neurodegenerative diseases and contribute to disease pathogenesis, since increased levels ameliorate behavioral defects and neuropathology of Huntington's disease, Parkinson's disease, and amyotrophic lateral sclerosis. PGC\u20101\u03b1 and its downstream targets are reduced both in postmortem brain tissue of patients with Alzheimer's disease (AD) and in transgenic mouse models of AD. Therefore, we investigated whether increased expression of PGC\u20101\u03b1 would exert beneficial effects in the Tg19959 transgenic mouse model of AD; Tg19959 mice express the human amyloid precursor gene (APP) with 2 familial AD mutations and develop increased \u03b2\u2010amyloid levels, plaque deposition, and memory deficits by 2\u20133 mo of age. Rather than an improvement, the cross of the Tg19959 mice with mice overexpressing human PGC\u20101\u03b1 exacerbated amyloid and tau accumulation. This was accompanied by an impairment of proteasome activity. PGC\u20101\u03b1 overexpression induced mitochondrial abnormalities, neuronal cell death, and an exacerbation of behavioral hyperactivity in the Tg19959 mice. These findings show that PGG1\u03b1 overexpression exacerbates the neuropathological and behavioral deficits that occur in transgenic mice with mutations in APP that are associated with human AD.\u2014Dumont, M., Stack, C., Elipenahli, C., Jainuddin, S., Launay, N., Gerges, M., Starkova, N., Starkov, A. A., Calingasan, N. Y., Tampellini, D., Pujol, A, Beal, M. F. PGGla overexpression exacerbates \u03b2\u2010amyloid and tau deposition in a transgenic mouse model of Alzheimer's disease.\n                    <jats:italic>FASEB J.<\/jats:italic>\n                    28, 28\u20131745 (1755).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.13-236331","type":"journal-article","created":{"date-parts":[[2014,1,8]],"date-time":"2014-01-08T00:56:02Z","timestamp":1389142562000},"page":"1745-1755","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":47,"title":["PGC\u20101\u03b1: overexpression exacerbates \u03b2\u2010amyloid and tau deposition in a transgenic mouse model of Alzheimer's disease"],"prefix":"10.1096","volume":"28","author":[{"given":"Magali","family":"Dumont","sequence":"first","affiliation":[{"name":"Department of Neurology and Neuroscience Weill Cornell Medical College New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cliona","family":"Stack","sequence":"additional","affiliation":[{"name":"Department of Neurology and Neuroscience Weill Cornell Medical College New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ceyhan","family":"Elipenahli","sequence":"additional","affiliation":[{"name":"Department of Neurology and Neuroscience Weill Cornell Medical College New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shari","family":"Jainuddin","sequence":"additional","affiliation":[{"name":"Department of Neurology and Neuroscience Weill Cornell Medical College New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathalie","family":"Launay","sequence":"additional","affiliation":[{"name":"Neurometabolic Diseases Laboratory Institute of Neuropathology, Bellvitge Biomedical Research Institute (IDIBELL), Hospital Duran i Reynals, L'Hospitalet de Llobregat Barcelona Spain"},{"name":"Center for Biomedical Research on Rare Diseases (CIBERER), U579 Instituto de Salud Carlos III (ISCIII) Valencia Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meri","family":"Gerges","sequence":"additional","affiliation":[{"name":"Department of Neurology and Neuroscience Weill Cornell Medical College New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia","family":"Starkova","sequence":"additional","affiliation":[{"name":"Department of Neurology and Neuroscience Weill Cornell Medical College New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anatoly A.","family":"Starkov","sequence":"additional","affiliation":[{"name":"Department of Neurology and Neuroscience Weill Cornell Medical College New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noel Y.","family":"Calingasan","sequence":"additional","affiliation":[{"name":"Department of Neurology and Neuroscience Weill Cornell Medical College New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Davide","family":"Tampellini","sequence":"additional","affiliation":[{"name":"Hospital Kremlin Bic\u00eatre Unit\u00e9 Mixte de Recherche (UMR) 788 Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale (INSERM), Universit\u00e9 Paris Sud Le Kremlin Bic\u00eatre France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aurora","family":"Pujol","sequence":"additional","affiliation":[{"name":"Neurometabolic Diseases Laboratory Institute of Neuropathology, Bellvitge Biomedical Research Institute (IDIBELL), Hospital Duran i Reynals, L'Hospitalet de Llobregat Barcelona Spain"},{"name":"Center for Biomedical Research on Rare Diseases (CIBERER), U579 Instituto de Salud Carlos III (ISCIII) Valencia Spain"},{"name":"Catalan Institution for Research and Advanced Studies (ICREA) Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. 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