The glycoprotein GPNMB is selectively elevated in the substantia nigra of Parkinson's disease patients and increases after lysosomal stress

Neurobiology of Disease
Elizabeth B MoloneyPenelope J Hallett

Abstract

GPNMB is a glycoprotein observed upon tissue damage and inflammation and is associated with astrocytes, microglia, and macrophages. Gene variations in GPNMB are linked with Parkinson's disease (PD) risk, and changes in protein levels of GPNMB have been found in lysosomal storage disorders, including Gaucher's disease with glucocerebrosidase (GCase) deficiency. In the current study, GPNMB increases were seen in the substantia nigra (SN) of PD patients compared to age-matched controls. Such PD patients have a decrease in GCase activity and corresponding elevation of glycosphingolipids in the SN (Rocha et al., 2015a). Interestingly, transgenic mice modelling synucleinopathy did not show GPNMB elevations or altered GCase activity levels compared to wild-type mice. However, upon CBE-induced GCase lysosomal dysfunction with elevated glycosphingolipids in wild-type mice, there were similar changes in GPNMB levels in the brain as seen in PD patient brains. These results indicate that GPNMB levels do not depend on alpha-synuclein load per se but relate directly to the lipidopathy changes induced by CBE-mediated GCase inhibition. The experimental modelling of elevating glycolipids resulted in GPNMB elevations with glial activation in sev...Continue Reading

References

Sep 1, 1996·QJM : Monthly Journal of the Association of Physicians·O NeudorferA Zimran
Jul 6, 2004·Molecular Genetics and Metabolism·Kondi WongRaphael Schiffmann
May 4, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Vera M RipollDavid A Hume
Oct 20, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Jin-Sung ChungKiyoshi Ariizumi
Oct 23, 2009·The New England Journal of Medicine·E SidranskyS G Ziegler
Dec 3, 2010·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Michela DeleidiOle Isacson
May 19, 2011·Nature Reviews. Neuroscience·Timothy J CollierJeffrey H Kordower
May 28, 2011·Pathology International·Masanobu MomoseMasayoshi Hayama
Jul 7, 2011·Proceedings of the National Academy of Sciences of the United States of America·S Pablo SardiLamya S Shihabuddin
Jul 9, 2011·PLoS Genetics·UNKNOWN International Parkinson's Disease Genomics Consortium (IPDGC), UNKNOWN Wellcome Trust Case Control Consortium 2 (WTCCC2)
Aug 9, 2011·Biochimica Et Biophysica Acta·Candace M PfefferkornJennifer C Lee
Feb 22, 2012·Science Translational Medicine·Michela Deleidi, Ole Isacson
Feb 22, 2012·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Marie-Francoise ChesseletSudhakar R Subramaniam
May 3, 2012·Neurobiology of Disease·Penelope J HallettOle Isacson
Aug 15, 2012·Scientific Reports·Hirotaka TanakaHideaki Hara
Oct 5, 2012·Annals of Neurology·Matthew E GeggAnthony H V Schapira
Oct 20, 2012·Lancet Neurology·Ellen Sidransky, Grisel Lopez
Jul 5, 2013·Current Opinion in Neurology·Anthony H V Schapira
Nov 23, 2013·Parkinsonism & Related Disorders·Lama M ChahineAlice Chen-Plotkin
Jan 31, 2014·Brain : a Journal of Neurology·Karen E MurphyGlenda M Halliday
Jun 6, 2014·Nature·Frances M Platt
Jul 20, 2014·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Franziska RichterMarie-Françoise Chesselet
Dec 3, 2014·Neuroscience·N DzamkoG M Halliday
Apr 25, 2015·Annals of Clinical and Translational Neurology·Emily M RochaOle Isacson
Jun 24, 2015·Human Molecular Genetics·Ravindran Kumaran, Mark R Cookson
Feb 11, 2016·Journal of Neurochemistry·Judith Blanz, Paul Saftig
Apr 22, 2016·Nature Communications·Karpagam SrinivasanDavid V Hansen
Apr 30, 2016·Ageing Research Reviews·Didac Carmona-GutierrezChristoph Ruckenstuhl

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Citations

May 24, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Pei-Suen Tsou, Amr H Sawalha
May 22, 2020·Molecular Neurobiology·Kevin M BudgeFayez F Safadi
Jul 14, 2020·Frontiers in Neuroscience·Qiao MaoXingguang Luo
Nov 14, 2019·Journal of Molecular Neuroscience : MN·Shaochun ZhuMiles Trupp
Mar 19, 2020·Journal of Clinical Medicine·Daphne E C BoerJohannes M F G Aerts
Dec 28, 2018·International Journal of Molecular Sciences·Martijn J C van der LiendenMarco van Eijk
Jun 21, 2019·Intractable & Rare Diseases Research·Jun-Ichi SatohYuko Saito
Jul 25, 2019·Journal of Neuroinflammation·Penelope J HallettOle Isacson
Jan 9, 2021·PLoS Genetics·Denis A BairdUNKNOWN AMP-AD eQTL working group
Jan 10, 2021·Molecular Genetics and Metabolism·Gregory A GrabowskiPramod K Mistry
Oct 17, 2020·Proceedings of the National Academy of Sciences of the United States of America·Oeystein Roed BrekkOle Isacson
Mar 2, 2021·Journal of Parkinson's Disease·Konstantin SenkevichZiv Gan-Or
May 6, 2021·Alzheimer's Research & Therapy·Freyja AichholzerOliver Wirths
Jun 1, 2021·Frontiers in Immunology·Marina SaadePaula Fernanda Kinoshita
Jul 3, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Paul W ChrystalW Ted Allison
Sep 1, 2021·Neurobiology of Disease·Robert BrendzaBrad A Friedman
Dec 4, 2021·Nature Communications·Grace PngEleftheria Zeggini
Jan 16, 2022·Brain, Behavior, and Immunity·Akua A KarikariChi Wang Ip

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