PGC-1α Promoter Methylation in Parkinson's Disease

PloS One
Xiaomin SuHoward J Federoff

Abstract

The etiopathogenesis of sporadic Parkinson's disease (PD) remains elusive although mitochondrial dysfunction has long been implicated. Recent evidence revealed reduced expression of peroxisome proliferator-activated receptor gamma coactivator-1 α (PGC-1α) and downstream regulated nuclear encoded respiratory complex genes in affected brain tissue from PD patients. We sought to determine whether epigenetic modification of the PGC-1α gene could account for diminished expression. In substantia nigra from PD patients but not control subjects, we show significant promoter-proximal non-canonical cytosine methylation of the PGC-1α gene but not an adjacent gene. As neuroinflammation is a prominent feature of PD and a mediator of epigenetic change, we evaluated whether the pro-inflammatory fatty acid, palmitate, would stimulate PGC-1α promoter methylation in different cell types from the CNS. Indeed, in mouse primary cortical neurons, microglia and astrocytes, palmitate causes PGC-1α gene promoter non-canonical cytosine methylation, reduced expression of the gene and reduced mitochondrial content. Moreover, intracerebroventricular (ICV) injection of palmitate to transgenic human α-synuclein mutant mice resulted in increased PGC-1α promot...Continue Reading

References

Dec 1, 1989·Annals of Neurology·W D ParkerJ K Parks
Jul 1, 1997·Journal of Neurochemistry·P HomayounN G Bazan
Jan 14, 1999·Genes & Development·C P Walsh, T H Bestor
Jun 29, 1999·Journal of Nuclear Cardiology : Official Publication of the American Society of Nuclear Cardiology·E NicolaiM Salvatore
Feb 10, 2000·Nucleic Acids Research·C GrunauA Rosenthal
Jun 5, 2003·American Journal of Epidemiology·Honglei ChenAlberto Ascherio
Sep 16, 2003·Neuron·William Dauer, Serge Przedborski
Dec 6, 2003·Science·Tiago Fleming Outeiro, Susan Lindquist
Oct 6, 2004·Genome Biology·Robert C GentlemanJianhua Zhang
Jan 27, 2005·Journal of Neuroscience Research·Jian FengGuoping Fan
May 26, 2005·Cardiovascular Research·Inmaculada ValleMaría Monsalve
Aug 2, 2005·Cell Metabolism·Jiandie LinBruce M Spiegelman
Dec 13, 2005·Nature Clinical Practice. Oncology·Stephen B Baylin
Jan 26, 2007·Diabetes Care·Gang HuJaakko Tuomilehto
Jun 26, 2008·JAMA : the Journal of the American Medical Association·Hans T BjornssonAndrew P Feinberg
Mar 12, 2009·Current Opinion in Lipidology·Carles Cantó, Johan Auwerx
Oct 21, 2009·Neuron·Maria BjörkqvistSarah J Tabrizi
Jun 23, 2010·Diabetes·Anna KarmiPirjo Nuutila
Aug 13, 2010·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Jill K MorrisPaige C Geiger
Oct 12, 2010·Science Translational Medicine·Bin ZhengUNKNOWN Global PD Gene Expression (GPEX) Consortium
Feb 11, 2011·Nature·Ergün SahinRonald A DePinho
Oct 11, 2011·Cellular and Molecular Life Sciences : CMLS·Giuseppa MudòDan Lindholm
Nov 18, 2011·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Barry A ChestnutLee J Martin
Dec 1, 2011·Clinical and Experimental Pharmacology & Physiology·Ming Lu, Gang Hu
Mar 23, 2012·American Journal of Physiology. Endocrinology and Metabolism·Aaron C BaldwinJohn A Corbett
Jan 18, 2013·Genome Research·Katherine E VarleyRichard M Myers
Feb 5, 2013·Trends in Molecular Medicine·Jose A Santiago, Judith A Potashkin

❮ Previous
Next ❯

Citations

Mar 11, 2016·BMC Medical Genomics·Maykel Cruz-MonteagudoEduardo Tejera
Feb 6, 2017·Brain Research·Rita TorokPeter Klivenyi
Jan 25, 2018·Genes·Francesca MastropasquaMaria Shoshan
Apr 5, 2018·Current Neurology and Neuroscience Reports·Jin-Sung ParkCarolyn M Sue
Jan 10, 2019·Cells·Helena XicoyGerard J M Martens
Mar 16, 2019·Epigenetics : Official Journal of the DNA Methylation Society·Adrienne Henderson-SmithPaula Desplats
Apr 6, 2019·Journal of Neural Transmission·Rezzak YilmazDaniela Berg
Jul 18, 2019·Aging Cell·Gayoung LeeHunjoo Ha
Oct 21, 2016·American Journal of Physiology. Renal Physiology·Olga Ruiz-AndresAlberto Ortiz
Sep 30, 2018·Neurological Sciences : Official Journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology·Ramandeep KaurShamsher Singh
Sep 6, 2019·Oxidative Medicine and Cellular Longevity·Xue JiangYing Zhang
Jul 8, 2020·International Journal of Molecular Sciences·Aintzane Urbizu, Katrin Beyer
May 25, 2016·Clinical Science·Kirsten F Howlett, Sean L McGee
Aug 5, 2017·Frontiers in Molecular Neuroscience·Ernesto Miranda-MoralesOscar Arias-Carrión
Aug 21, 2018·Frontiers in Cellular Neuroscience·Mathilde Cheray, Bertrand Joseph
Sep 13, 2018·Metabolites·Massimo S FiandacaHoward J Federoff
Nov 7, 2019·International Journal of Molecular Sciences·Anne I Krämer, Christoph Handschin
Oct 3, 2017·Neural Regeneration Research·Chee-Hoe NgKah-Leong Lim
Oct 26, 2018·International Journal of Molecular Sciences·Zhengchang WuWenbin Bao
Jun 20, 2018·Molecular Neurobiology·Ana Ortiz-RodriguezLuis M Garcia-Segura
Apr 28, 2016·Journal of Neurochemistry·Ullrich WüllnerIna Schmitt
Jan 24, 2021·Molecular Neurobiology·Hong-Qiu ZhangJian-Hong Zhu
Mar 20, 2020·Journal of Medicinal Chemistry·Daniele PiomelliMarco Mor
Mar 7, 2021·Nutrients·Nathalie AcevedoBetty C A M van Esch
Sep 7, 2020·Mechanisms of Ageing and Development·Ioanna Daskalaki, Nektarios Tavernarakis
Apr 1, 2021·The International Journal of Neuroscience·Xin GuanYanqin Wang
Apr 4, 2021·International Journal of Molecular Sciences·Elena PiccininGaetano Villani
May 14, 2021·Frontiers in Genetics·Adrienne R HendersonTravis Dunckley
Jun 3, 2021·International Journal of Molecular Sciences·Madiha RasheedZixuan Chen
Jun 15, 2021·ACS Chemical Neuroscience·Prabitha PB R Prashantha Kumar
Jun 15, 2021·Frontiers in Cell and Developmental Biology·Bipul RayMeena Kishore Sakharkar
Jul 27, 2021·Frontiers in Aging Neuroscience·Upasana GangulySasanka Chakrabarti
Jul 17, 2021·Neural Regeneration Research·Jessica D PanesJorge Fuentealba
Jul 30, 2021·Science Translational Medicine·Areum JoJoo-Ho Shin
Jul 29, 2021·Neuropathology and Applied Neurobiology·Megha MurthyConceição Bettencourt

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Datasets Mentioned

BETA
GSE8397
GSE24378

Methods Mentioned

BETA
transgenic
PCR
protein assay
ELISA
Methylation sequencing

Software Mentioned

Fluoroview
MethTools
R
ImageJ
Bioconductor

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