Expression analysis of dopaminergic neurons in Parkinson's disease and aging links transcriptional dysregulation of energy metabolism to cell death.

Acta Neuropathologica
Matthias ElstnerHolger Prokisch

Abstract

Dopaminergic (DA) neuron degeneration is a feature of brain aging but is markedly increased in patients with Parkinson's disease (PD). Recent data indicate elevated metabolic stress as a possible explanation for DA neuron vulnerability. Using laser capture microdissection, we isolated DA neurons from the substantia nigra pars compacta of PD patients, age-matched and young controls to determine transcriptional changes by expression profiling and pathway analysis. We verified our findings by comparison to a published dataset. Parallel processing of isolated neurons and bulk tissue allowed the discrimination of neuronal and glial transcription signals. Our data show that genes known to be involved in neural plasticity, axon and synaptic function, as well as cell fate are differentially regulated in aging DA neurons. The transcription patterns in aging suggest a largely maintained expression of genes in energy-related pathways in surviving neurons, possibly supported by the mediation of PPAR/RAR and CREB signaling. In contrast, a profound down-regulation of genes coding for mitochondrial and ubiquitin--proteasome system proteins was seen in PD when compared to the age-matched controls. This is in accordance with the established mit...Continue Reading

References

Oct 1, 1991·Brain : a Journal of Neurology·J M Fearnley, A J Lees
Jan 21, 2001·The Journal of Biological Chemistry·T FujinoT T Yamamoto
Aug 15, 2002·Neuropathology and Applied Neurobiology·C R CabelloB Pakkenberg
Dec 25, 2002·Neurobiology of Aging·Heiko BraakEva Braak
Jul 29, 2003·The Journal of Biological Chemistry·Ei SekoguchiAkira Matsuura
Sep 16, 2003·Neuron·William Dauer, Serge Przedborski
Apr 29, 2004·Nature Neuroscience·Károly Mirnics, Jonathan Pevsner
Jun 11, 2004·Nature·Tao LuBruce A Yankner
Sep 15, 2004·Cell and Tissue Research·A K Stark, B Pakkenberg
Sep 25, 2004·Annals of Neurology·G Webster RossLon R White
Nov 13, 2004·Journal of Neuropathology and Experimental Neurology·Carlos BuesaIsidro Ferrer
Jun 21, 2005·American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics : the Official Publication of the International Society of Psychiatric Genetics·Yanli ZhangRichard L Davis
Sep 2, 2005·Nature·Steve E CalvanoUNKNOWN Inflamm and Host Response to Injury Large Scale Collab. Res. Program
Sep 7, 2005·Neurobiology of Disease·Renee M MillerHoward J Federoff
Oct 21, 2005·Neurology·I G McKeithUNKNOWN Consortium on DLB
Feb 24, 2006·Nature Reviews. Neuroscience·Patrick M Abou-SleimanNicholas W Wood
Mar 18, 2006·Nature Reviews. Genetics·Matthew James Farrer
Apr 22, 2006·Experimental Neurology·Ina R VogtUllrich Wüllner
Jun 22, 2006·Neurotoxicity Research·M GerlachP Riederer
Apr 7, 2007·Neurobiology of Disease·Ippolita Cantuti-CastelvetriDavid G Standaert
May 22, 2007·Journal of Neuroscience Methods·Mary AtzUNKNOWN Members of National Institute of Mental Health Conte Center and Pritzker Neuropsychiatric Disorders Research Consortium
Jun 15, 2007·Nature·C Savio ChanD James Surmeier
Jun 19, 2007·PLoS Genetics·Timothy G LesnickDemetrius M Maraganore
Sep 22, 2007·Lancet Neurology·D James Surmeier
Feb 26, 2008·Acta Neuropathologica·Gay RudowJuan C Troncoso
Mar 19, 2008·Acta Neuropathologica·Manuel B Graeber
Jul 1, 2008·Parkinsonism & Related Disorders·P RiedererE Grünblatt
Jul 8, 2008·Journal of Neurology·Andreas BenderThomas Klopstock
Jul 9, 2008·Current Opinion in Neurology·Alexis Elbaz, Frédéric Moisan
Jul 16, 2008·Free Radical Biology & Medicine·Ana F DominguesSandra M Cardoso
Jul 30, 2008·Experimental Gerontology·Guillermo López-LluchRafael de Cabo
Sep 23, 2008·Metabolism: Clinical and Experimental·Theodore B Vanitallie
Oct 9, 2008·Neurochemical Research·C David Rollo
Oct 11, 2008·Journal of Cellular Biochemistry·Carolyn M Klinge
Oct 17, 2008·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·C Anthony AltarStephen D Ginsberg
Oct 22, 2008·Biochimica Et Biophysica Acta·Natalia B NedelskyJ Paul Taylor

❮ Previous
Next ❯

Citations

Aug 15, 2012·Nature Reviews. Neurology·Johnathan Cooper-KnockPamela J Shaw
May 3, 2013·PloS One·Lin GaoAlberto Pascual
Jun 21, 2013·Kidney International·Sam H TryggvasonLiqun He
Jun 20, 2012·Progress in Neurobiology·Gang WangSheng-Di Chen
Jun 12, 2014·Journal of Neuropathology and Experimental Neurology·Mariona JovéReinald Pamplona
Jun 13, 2015·Mechanisms of Ageing and Development·Gemma M ParkinsonDoug W Smith
Jul 28, 2016·Translational Neurodegeneration·Qingsong Hu, Guanghui Wang
Feb 14, 2015·Molecular Neurobiology·Cornelius J H M KlemannJasper E Visser
Jan 27, 2017·Molecular Neurodegeneration·Tim E MoorsWilma D J van de Berg
Nov 15, 2017·Molecular Neurodegeneration·Karim BelarbiMarie-Christine Chartier-Harlin
Apr 6, 2018·Nature Reviews. Molecular Cell Biology·Ivan Dikic, Zvulun Elazar
Sep 13, 2018·Annual Review of Pharmacology and Toxicology·Miguel MoutinhoGary E Landreth
Sep 26, 2012·Movement Disorders : Official Journal of the Movement Disorder Society·J Paul Bolam, Eleftheria K Pissadaki
Nov 15, 2011·Movement Disorders : Official Journal of the Movement Disorder Society·Kurt A Jellinger
May 21, 2017·Experimental Brain Research·Abhishek Singh, Dwaipayan Sen
Sep 6, 2019·Oxidative Medicine and Cellular Longevity·Xue JiangYing Zhang
Oct 27, 2017·The European Journal of Neuroscience·Genevie BorrageiroSoraya Bardien
Jan 30, 2018·Frontiers in Molecular Neuroscience·Adam LabadorfRichard H Myers
Feb 2, 2019·Neurotoxicity Research·Sachchida Nand RaiSurya Pratap Singh
Apr 23, 2020·Acta Neuropathologica Communications·Gonzalo S NidoCharalampos Tzoulis
Jan 18, 2020·Biomolecules·Antonia CianciulliMaria Antonietta Panaro
May 13, 2018·Genes·Mario Rango, Nereo Bresolin
Jul 12, 2020·Antioxidants·Kuo-Hsuan Chang, Chiung-Mei Chen
May 28, 2019·Frontiers in Neuroscience·Šárka LehtonenJari Koistinaho
Oct 23, 2020·Metabolic Brain Disease·Tanvi Pingale, Girdhari Lal Gupta
Sep 2, 2020·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Seyede Nazanin ZarneshanLuciano Saso
Mar 14, 2020·Annals of Neurology·Jimena Monzón-SandovalLaura Parkkinen

❮ Previous
Next ❯

Related Concepts

Related Feeds

AKT Pathway

This feed focuses on the AKT serine/threonine kinase, which is an important signaling pathway involved in processes such as glucose metabolism and cell survival.

Basal Ganglia

Basal Ganglia are a group of subcortical nuclei in the brain associated with control of voluntary motor movements, procedural and habit learning, emotion, and cognition. Here is the latest research.