Excess α-synuclein worsens disease in mice lacking ubiquitin carboxy-terminal hydrolase L1.

Scientific Reports
Derya R ShimshekP Herman van der Putten

Abstract

Mutations in α-synuclein (αSN) and ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) have been linked to familial Parkinson's disease (PD). Physical and functional interactions between these two proteins have been described. Whether they act additively in vivo to influence disease has remained controversial. αSN is a presynaptic protein and the major constituent of Lewy inclusions, histopathological hallmarks of PD. UCH-L1 regulates ubiquitin stability in the nervous system and its loss results in neurodegeneration in peripheral and central neurons. Here, we used genetics to show that UCH-L1-deficiency together with excess αSN worsen disease. Double mutant mice show earlier-onset motor deficits, a shorter lifespan and forebrain astrogliosis but the additive disease-worsening effects of UCH-L1-deficiency and excess αSN are not accompanied by microgliosis, ubiquitin pathology or changes in pathological αSN protein levels and species.

References

Jan 1, 1987·The Journal of Physiology·K BallanyiG ten Bruggencate
Feb 1, 1988·Proceedings of the Society for Experimental Biology and Medicine·K YamazakiK Ando
Mar 1, 1994·Veterinary Pathology·D L Montgomery
Aug 28, 1997·Nature·M G SpillantiniM Goedert
Apr 18, 1998·Neuroscience Letters·K WakabayashiH Takahashi
Oct 17, 1998·Nature·E LeroyM H Polymeropoulos
Apr 4, 2000·Nature·M B Feany, W W Bender
Sep 14, 2001·Human Molecular Genetics·L J KuriharaS M Tilghman
Jun 27, 2002·Proceedings of the National Academy of Sciences of the United States of America·Michael K LeeDon L Price
Dec 31, 2002·Experimental Neurology·Kevin St P McNaughtC Warren Olanow
Feb 26, 2003·Proceedings of the National Academy of Sciences of the United States of America·Deniz KirikAnders Björklund
Apr 1, 2003·Annals of Neurology·Kevin St P McNaught, C Warren Olanow
Jun 20, 2003·Neuropharmacology·Kumlesh K DevHerman van der Putten
Jun 24, 2003·The American Journal of Pathology·Deepak M SampathuVirginia M-Y Lee
Aug 13, 2003·Human Molecular Genetics·Hitoshi OsakaKeiji Wada
Nov 1, 2003·Science·A B SingletonK Gwinn-Hardy
Feb 3, 2004·Annals of Neurology·Juan J ZarranzJusto G de Yebenes
Mar 30, 2004·Annals of Neurology·Demetrius M MaraganoreUNKNOWN UCHL1 Global Genetics Consortium
Oct 29, 2004·The EMBO Journal·Shumin LiuOttavio Arancio
Mar 2, 2005·Pharmacology & Therapeutics·M Catherine Bennett
Nov 5, 2005·Cell·Sreeganga ChandraThomas C Südhof
Dec 29, 2005·Neurobiology of Disease·Marta BarrachinaIsidro Ferrer
Feb 2, 2006·Annals of Neurology·Daniel G HealyNicholas W Wood
Aug 16, 2006·Neuro-degenerative Diseases·Helen C Ardley, Philip A Robinson
Aug 18, 2006·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Derya R ShimshekRolf Sprengel
Sep 15, 2006·Movement Disorders : Official Journal of the Movement Disorder Society·C Warren Olanow, Kevin St P McNaught
Dec 21, 2006·Neuroreport·Agata Adamczyk, Joanna B Strosznajder
Jun 15, 2007·Expert Review of Neurotherapeutics·Ennio EspositoGiuseppe Di Giovanni
Sep 6, 2008·Molecular and Cellular Neurosciences·B J WaltersS M Wilson

❮ Previous
Next ❯

Citations

Oct 16, 2014·Proceedings of the National Academy of Sciences of the United States of America·Michelle RothaugJudith Blanz
Aug 28, 2013·Neuromolecular Medicine·Katrin Eckermann
Dec 18, 2014·Annals of the New York Academy of Sciences·Jorge S ValadasPatrik Verstreken
Nov 21, 2017·Acta Neuropathologica·Peizhou Jiang, Dennis W Dickson
Jun 19, 2019·Cell Death and Differentiation·Tony ValenteJosep Saura
Jan 14, 2018·Neurobiology of Disease·Kunikazu TanjiKoichi Wakabayashi

❮ Previous
Next ❯

Methods Mentioned

BETA
transgenic
PCR

Related Concepts

Related Feeds

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.