Methylation Regulates Alpha-Synuclein Expression and Is Decreased in Parkinson's Disease Patients' Brains

被引：322
作者：
Jowaed, Ahmad [1 ]
Schmitt, Ina [1 ]
Kaut, Oliver [1 ]
Wuellner, Ullrich [1 ]
机构：
[1] Univ Bonn, Dept Neurol, Univ Klinikum Bonn, D-53105 Bonn, Germany
来源：
JOURNAL OF NEUROSCIENCE | 2010年 / 30卷 / 18期
关键词：
DNA METHYLATION; MESSENGER-RNA; GENE; PROMOTER; CORTEX;
D O I：
10.1523/JNEUROSCI.6119-09.2010
中图分类号：
Q189 [神经科学];
学科分类号：
071006 ;
摘要：
Alpha-synuclein (SNCA) is a major risk gene for Parkinson's disease (PD), and increased SNCA gene dosage results in a parkinsonian syndrome in affected families. We found that methylation of human SNCA intron 1 decreased gene expression, while inhibition of DNA methylation activated SNCA expression. Methylation of SNCA intron 1 was reduced in DNA from sporadic PD patients' substantia nigra, putamen, and cortex, pointing toward a yet unappreciated epigenetic regulation of SNCA expression in PD.
引用
收藏
页码：6355 / 6359
页数：5
相关论文
共 24 条
  • [1] Staging of brain pathology related to sporadic Parkinson's disease
    Braak, H
    Del Tredici, K
    Rüb, U
    de Vos, RAI
    Steur, ENHJ
    Braak, E
    [J]. NEUROBIOLOGY OF AGING, 2003, 24 (02) : 197 - 211
  • [2] The story of Rett syndrome: From clinic to neurobiology
    Chahrour, Maria
    Zoghbi, Huda Y.
    [J]. NEURON, 2007, 56 (03) : 422 - 437
  • [3] Levels of alpha-synuclein mRNA in sporadic Parkinson disease patients
    Chiba-Falek, Ornit
    Lopez, Grisel J.
    Nussbaum, Robert L.
    [J]. MOVEMENT DISORDERS, 2006, 21 (10) : 1703 - 1708
  • [4] Aging and Environmental Exposures Alter Tissue-Specific DNA Methylation Dependent upon CpG Island Context
    Christensen, Brock C.
    Houseman, E. Andres
    Marsit, Carmen J.
    Zheng, Shichun
    Wrensch, Margaret R.
    Wiemels, Joseph L.
    Nelson, Heather H.
    Karagas, Margaret R.
    Padbury, James F.
    Bueno, Raphael
    Sugarbaker, David J.
    Yeh, Ru-Fang
    Wiencke, John K.
    Kelsey, Karl T.
    [J]. PLOS GENETICS, 2009, 5 (08):
  • [5] A novel pathway for transcriptional regulation of α-synuclein
    Clough, R. Lee
    Stefanis, Leonidas
    [J]. FASEB JOURNAL, 2007, 21 (02) : 596 - 607
  • [6] Tissue-specific variation in DNA methylation levels along human chromosome 1
    De Bustos, Cecilia
    Ramos, Edward
    Young, Janet M.
    Tran, Robert K.
    Menzel, Uwe
    Langford, Cordelia F.
    Eichler, Evan E.
    Hsu, Li
    Henikoff, Steve
    Dumanski, Jan P.
    Trask, Barbara J.
    [J]. EPIGENETICS & CHROMATIN, 2009, 2
  • [7] Genome-Wide Association Study Confirms SNPs in SNCA and the MAPT Region as Common Risk Factors for Parkinson Disease
    Edwards, Todd L.
    Scott, William K.
    Almonte, Cherylyn
    Burt, Amber
    Powell, Eric H.
    Beecham, Gary W.
    Wang, Liyong
    Zuchner, Stephan
    Konidari, Ioanna
    Wang, Gaofeng
    Singer, Carlos
    Nahab, Fatta
    Scott, Burton
    Stajich, Jeffrey M.
    Pericak-Vance, Margaret
    Haines, Jonathan
    Vance, Jeffery M.
    Martin, Eden R.
    [J]. ANNALS OF HUMAN GENETICS, 2010, 74 : 97 - 109
  • [8] Phenotypic plasticity and the epigenetics of human disease
    Feinberg, Andrew P.
    [J]. NATURE, 2007, 447 (7143) : 433 - 440
  • [9] Elevated α-synuclein mRNA levels in individual UV-laser-microdissected dopaminergic substantia nigra neurons in idiopathic Parkinson's disease
    Gruendemann, Jan
    Schlaudraff, Falk
    Haeckel, Olga
    Liss, Birgit
    [J]. NUCLEIC ACIDS RESEARCH, 2008, 36 (07)
  • [10] Kaut O., 2009, Society for Neuroscience Abstract Viewer and Itinerary Planner, V39
123