title: Parkinson's disease: SNCA-, PARK2-, and LRRK2- targeting microRNAs elevated in cingulate gyrus.
abstract: In order to better understand the role of epigenetic influences in the etiology of Parkinson's disease (PD), we studied the expression of microRNAs in gyri cinguli of patients and controls.
  
  
  
  Expression profiling of 744 well-characterized microRNAs in gyri cinguli from patients and controls using TaqMan array microRNA cards. Verification of significantly dysregulated microRNAs by SYBR Green qRT-PCR.
  
  
  
  First screen by TaqMan array identified 43 microRNAs that were upregulated in gyri cinguli from patients. Of those microRNAs, 13 are predicted to regulate at least one of six genes mutated in monogenic forms of PD (DJ-1, PARK2, PINK1, LRRK2, SNCA, and HTRA2). Five of these 13 microRNAs (-144, -199b, -221, -488, -544) were also found upregulated by SYBR Green qRT-PCR and are predicted to regulate either SNCA, PARK2, LRRK2 or combinations thereof. Consistently, expression of SNCA, PARK2, and LRRK2 was reduced in patients. An additional 5 out of ten potential target genes tested were downregulated. These are DRAM (DNA damage regulated autophagy modulator 1), predicted to be regulated by miR-144, EVC (Ellis Van Creveld Protein) by miR-221, ZNF440 (Zinc Finger Protein 440) by miR-199b, MTFMT (Mitochondrial Methionyl-tRNA Formyltransferase) by miR-488 and XIRP2 (Xin Actin Binding Repeat Containing) possibly controlled by miR-544a.
  
  
  
  The study identified five microRNAs that play a role in the etiology of Parkinson's disease likely by modifying expression of SNCA, PARK2, LRRK2 and additional genes required for normal cellular function.
authors.affiliation: Institute of Human Genetics, Justus-Liebig-University, Schlangenzahl 14, Gießen, Germany.
authors.forename: Roman
authors.initials: R
authors.lastname: Tatura
authors.affiliation: Center for Neuropathology and Prion Research (ZNP), Ludwig Maximilians-University Munich, Feodor-Lynen-Str. 23, München, Germany.
authors.forename: Theo
authors.initials: T
authors.lastname: Kraus
authors.affiliation: Center for Neuropathology and Prion Research (ZNP), Ludwig Maximilians-University Munich, Feodor-Lynen-Str. 23, München, Germany.
authors.forename: Armin
authors.initials: A
authors.lastname: Giese
authors.affiliation: Center for Neuropathology and Prion Research (ZNP), Ludwig Maximilians-University Munich, Feodor-Lynen-Str. 23, München, Germany; Department of Psychiatry and Psychotherapy, Ludwig-Maximilians-University Munich, Nussbaumstraße 7, Munich, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Arzberger
authors.affiliation: Clinic for Gastroenterology, Endocrinology and Metabolism, Philipps-University, Baldingerstrasse, Marburg, Germany.
authors.forename: Malte
authors.initials: M
authors.lastname: Buchholz
authors.affiliation: Department of Neurology, Technical University of Munich and German Center for Neurodegenerative Diseases e.V. (DZNE) Munich, Feodor-Lynen Str. 17, Munich, Germany.
authors.forename: Günter
authors.initials: G
authors.lastname: Höglinger
authors.affiliation: Institute of Human Genetics, Justus-Liebig-University, Schlangenzahl 14, Gießen, Germany. Electronic address: ulrich.mueller@med.uni-giessen.de.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Müller
mesh_terms: D000368:Aged; D005260:Female; D005786:Gene Expression Regulation / Q000235:genetics*; D006179:Gyrus Cinguli / Q000378:metabolism*; D006801:Humans; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 / Q000235:genetics*; D008297:Male; D035683:MicroRNAs; D008875:Middle Aged; D010300:Parkinson Disease / Q000235:genetics* / Q000473:pathology*; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*; D051844:alpha-Synuclein / Q000235:genetics*
chemical_list: D035683:MicroRNAs; C497604:SNCA protein, human; D051844:alpha-Synuclein; D044767:Ubiquitin-Protein Ligases; C111567:parkin protein; C495280:LRRK2 protein, human; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2
keywords: LRRK2; PARK2; Parkinson's disease; SNCA; TaqMan; miR-144; miR-199b; miR-221; miR-488; miR-544