Paula Garcia-Esparcia1,2, Karina Hernández-Ortega1, Belén Ansoleaga1, Margarita Carmona1,2, Isidre Ferrer1,2,3. 1. Institute of Neuropathology, Bellvitge University Hospital-Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain. 2. Center for Networked Biomedical Research in Neurodegenerative Diseases (CIBERNED), Institute Carlos III, Ministry of Health, Barcelona, Spain. 3. University of Barcelona, Barcelona, Spain.
Abstract
AIMS: To explore alterations in the expression of genes encoding enzymes involved in purine metabolism in Parkinson's disease (PD) brains as purines are the core of the DNA, RNA, nucleosides and nucleotides which participate in a wide variety of crucial metabolic pathways. METHODS: Analysis of mRNA using real-time quantitative PCR of 22 genes involved in purine metabolism in the substantia nigra, putamen and cerebral cortex area 8 in PD at different stages of disease progression, and localization of selected purine metabolism-related enzymes with immunohistochemistry. RESULTS: Reduced expression of adenylate kinase 2 (AKA2), AK3, AK4, adenine phosphoribosyltransferase, ectonucleoside triphosphate diphosphohydrolase 1 (ENTPD1), ENTPD3, nonmetastatic cells 3, nucleoside-diphosphatese kinase 3 (NME1), NME7 and purine nucleoside phosphorylase 1 (PNP1) mRNA in the substantia nigra at stages 3-6; up-regulation of ADA mRNA in the frontal cortex area 8 at stages 3-4 and of AK1, AK5, NME4, NME5, NME6, 5'-nucleotidase (NT5E), PNP1 and prune homolog Drosophila at stages 5-6. There is no modification in the expression of these genes in the putamen at stages 3-5. CONCLUSIONS: Gene down-regulation in the substantia nigra may be interpreted as a consequence of dopaminergic cell death as ENTPD3, NME1, NME7, AK1 and PNP1 are mainly expressed in neurons. Yet ENTPD1 and NT5E, also down-regulated in the substantia nigra, are expressed in astrocytes, probably pericytes and microglia, respectively. In contrast, gene up-regulation in the frontal cortex area 8 at advanced stages of the disease suggests a primary manifestation or a compensation of altered purine metabolism in this region.
AIMS: To explore alterations in the expression of genes encoding enzymes involved in purine metabolism in Parkinson's disease (PD) brains as purines are the core of the DNA, RNA, nucleosides and nucleotides which participate in a wide variety of crucial metabolic pathways. METHODS: Analysis of mRNA using real-time quantitative PCR of 22 genes involved in purine metabolism in the substantia nigra, putamen and cerebral cortex area 8 in PD at different stages of disease progression, and localization of selected purine metabolism-related enzymes with immunohistochemistry. RESULTS: Reduced expression of adenylate kinase 2 (AKA2), AK3, AK4, adenine phosphoribosyltransferase, ectonucleoside triphosphate diphosphohydrolase 1 (ENTPD1), ENTPD3, nonmetastatic cells 3, nucleoside-diphosphatese kinase 3 (NME1), NME7 and purine nucleoside phosphorylase 1 (PNP1) mRNA in the substantia nigra at stages 3-6; up-regulation of ADA mRNA in the frontal cortex area 8 at stages 3-4 and of AK1, AK5, NME4, NME5, NME6, 5'-nucleotidase (NT5E), PNP1 and prune homolog Drosophila at stages 5-6. There is no modification in the expression of these genes in the putamen at stages 3-5. CONCLUSIONS: Gene down-regulation in the substantia nigra may be interpreted as a consequence of dopaminergic cell death as ENTPD3, NME1, NME7, AK1 and PNP1 are mainly expressed in neurons. Yet ENTPD1 and NT5E, also down-regulated in the substantia nigra, are expressed in astrocytes, probably pericytes and microglia, respectively. In contrast, gene up-regulation in the frontal cortex area 8 at advanced stages of the disease suggests a primary manifestation or a compensation of altered purine metabolism in this region.
Authors: Euijung Ryu; Malik Nassan; Gregory D Jenkins; Sebastian M Armasu; Ana Andreazza; Susan L McElroy; Marquis P Vawter; Mark A Frye; Joanna M Biernacka Journal: Mol Neuropsychiatry Date: 2017-10-28
Authors: Nicholas J Fiore; Yosif M Ganat; Kapil Devkota; Rebecca Batorsky; Ming Lei; Kyongbum Lee; Lenore J Cowen; Gist Croft; Scott A Noggle; Thomas J F Nieland; David L Kaplan Journal: Cell Mol Life Sci Date: 2022-01-19 Impact factor: 9.261
Authors: Celia Kun-Rodrigues; Tatiana Orme; Susana Carmona; Dena G Hernandez; Owen A Ross; John D Eicher; Claire Shepherd; Laura Parkkinen; Lee Darwent; Michael G Heckman; Sonja W Scholz; Juan C Troncoso; Olga Pletnikova; Ted Dawson; Liana Rosenthal; Olaf Ansorge; Jordi Clarimon; Alberto Lleo; Estrella Morenas-Rodriguez; Lorraine Clark; Lawrence S Honig; Karen Marder; Afina Lemstra; Ekaterina Rogaeva; Peter St George-Hyslop; Elisabet Londos; Henrik Zetterberg; Imelda Barber; Anne Braae; Kristelle Brown; Kevin Morgan; Claire Troakes; Safa Al-Sarraj; Tammaryn Lashley; Janice Holton; Yaroslau Compta; Vivianna Van Deerlin; Geidy E Serrano; Thomas G Beach; Suzanne Lesage; Douglas Galasko; Eliezer Masliah; Isabel Santana; Pau Pastor; Monica Diez-Fairen; Miquel Aguilar; Pentti J Tienari; Liisa Myllykangas; Minna Oinas; Tamas Revesz; Andrew Lees; Brad F Boeve; Ronald C Petersen; Tanis J Ferman; Valentina Escott-Price; Neill Graff-Radford; Nigel J Cairns; John C Morris; Stuart Pickering-Brown; David Mann; Glenda M Halliday; John Hardy; John Q Trojanowski; Dennis W Dickson; Andrew Singleton; David J Stone; Rita Guerreiro; Jose Bras Journal: Neurobiol Aging Date: 2018-10-24 Impact factor: 4.673