Transcriptional dysregulation in a transgenic model of Parkinson disease

Neurobiology of Disease
T A YacoubianD G Standaert

Abstract

Alpha-synuclein has been implicated in Parkinson disease, yet the mechanism by which alpha-synuclein causes cell injury is not understood. Using a transgenic mouse model, we evaluated the effect of alpha-synuclein overexpression on gene expression in the substantia nigra. Nigral mRNA from wild type and alpha-synuclein transgenic mice was analyzed using Affymetrix gene arrays. At 3 months, before pathological changes are apparent, we observed modest alterations in gene expression. However, nearly 200 genes were altered in expression at 9 months, when degenerative changes are more apparent. Functional genomic analysis revealed that the genes altered at 9 months were predominantly involved in gene transcription. As in human Parkinson disease, gene expression changes in the transgenic model were also modulated by gender. These data demonstrate that alterations of gene expression are widespread in this animal model, and suggest that transcriptional dysregulation may be a disease mechanism that can be targeted therapeutically.

References

Jul 21, 1998·Annals of the New York Academy of Sciences·D B MillerS C Laws
Nov 11, 1998·Nature Medicine·L FinkR M Bohle
Dec 9, 1998·Proceedings of the National Academy of Sciences of the United States of America·M B EisenD Botstein
Apr 20, 2001·Proceedings of the National Academy of Sciences of the United States of America·V G TusherG Chu
Feb 16, 2002·Methods : a Companion to Methods in Enzymology·K J Livak, T D Schmittgen
Jul 12, 2002·Genetic Epidemiology·Bradley Efron, Robert Tibshirani
Nov 28, 2002·Nature Genetics·John Quackenbush
Jun 5, 2003·American Journal of Epidemiology·Stephen K Van Den EedenLorene M Nelson
Jul 3, 2003·Annals of Neurology·Daniela BergAntje Bornemann
Jul 16, 2003·Biochemistry·John GoersAnthony L Fink
Sep 11, 2003·Amyloid : the International Journal of Experimental and Clinical Investigation : the Official Journal of the International Society of Amyloidosis·Nikolaos K Robakis
Oct 30, 2003·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Marquis P VawterWilliam E Bunney
Nov 1, 2003·Science·A B SingletonK Gwinn-Hardy
Dec 23, 2003·Journal of Neuroscience Methods·Ramana V Gutala, P Hemachandra Reddy
Jan 7, 2004·Biochemical and Biophysical Research Communications·Aleksandar RadonićAndreas Nitsche
Feb 13, 2004·Bioinformatics·Leslie M CopeTerence P Speed
Apr 11, 2006·Journal of Neural Transmission·C K WangY R Wu
Apr 7, 2007·Neurobiology of Disease·Ippolita Cantuti-CastelvetriDavid G Standaert

❮ Previous
Next ❯

Citations

May 12, 2011·Mammalian Genome : Official Journal of the International Mammalian Genome Society·Paul M A AntonyRudi Balling
Apr 21, 2010·Cellular and Molecular Neurobiology·Yuhe YuanNai-Hong Chen
Aug 6, 2013·Journal of Molecular Neuroscience : MN·Huiping DingTalene A Yacoubian
Mar 10, 2012·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Paige M DexterGuy A Caldwell
Dec 15, 2010·Cell Death & Disease·T A YacoubianD G Standaert
Feb 8, 2011·The Journal of Biological Chemistry·Paula DesplatsEliezer Masliah
May 20, 2011·Database : the Journal of Biological Databases and Curation·Cristian TaccioliElia Stupka
Sep 19, 2014·Biogerontology·Danae Campos-MeloMichael J Strong
Aug 16, 2011·Brain Research Bulletin·Donna M Crabtree, Jianhua Zhang
Nov 8, 2015·Human Molecular Genetics·Nicholas J LavalleyTalene A Yacoubian
Nov 26, 2010·Journal of Neurochemistry·Trent U SteidingerTalene A Yacoubian
Dec 23, 2011·Annals of Neurology·Michael A van EsLeonard H van den Berg
Sep 26, 2015·Journal of Parkinson's Disease·Nadine BrehmGeorg Auburger
Jan 15, 2014·Biochimica Et Biophysica Acta·Rosanna Parlato, Birgit Liss
Oct 15, 2013·Cell Reports·Hojjat BazzaziDavid T Yue
Oct 22, 2008·Biochimica Et Biophysica Acta·Talene A Yacoubian, David G Standaert
Oct 16, 2016·Journal of Applied Microbiology·F Khan, S F Oloketuyi
Sep 17, 2018·Human Molecular Genetics·Raquel PinhoTiago F Outeiro
Oct 1, 2018·The European Journal of Neuroscience·Noémie CrestoEmmanuel Brouillet
Aug 14, 2020·International Journal of Molecular Sciences·C Alejandra Morato TorresBirgitt Schüle
Jan 9, 2021·Acta Neuropathologica Communications·Rachel UnderwoodTalene A Yacoubian
Apr 30, 2010·Disease Models & Mechanisms·David G Standaert, Talene A Yacoubian

❮ Previous
Next ❯

Related Concepts

Related Feeds

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.

Alpha-Synuclein Aggregation (MDS)

Alpha-synucleins are small proteins that are believed to restrict the mobility of synpatic vesicles and inhibit neurotransmitter release. Aggregation of these proteins have been linked to several types of neurodegenerative diseases including dementia with Lewy bodies and Parkinson's disease. Here is the latest research on α-synuclein aggregation.