Therapeutic Potential of a Prolyl Hydroxylase Inhibitor FG-4592 for Parkinson's Diseases in Vitro and in Vivo : Regulation of Redox Biology and Mitochondrial Function

Frontiers in Aging Neuroscience
Xuan LiYun-Cheng Wu

Abstract

As the main transcription factor that regulates the cellular responses to hypoxia, Hypoxia-inducible factor-1α (HIF-1α) plays an important role in the pathogenesis of Parkinson's disease (PD). HIF-1α is normally degraded through ubiquitination after hydroxylation by prolyl hydroxylases (PHD). Emerging evidence has suggested that HIF PHD inhibitors (HIF-PHI) may have neuroprotective effects on PD through increasing HIF-1α levels. However, the therapeutic benefit of HIF-PHI for PD remains poorly explored due to the lack of proper clinical compounds and understanding of the underlying molecular mechanisms. In this study, we examined the therapeutic benefit of a new HIF-PHI, FG-4592, which is currently in phase 3 clinical trials to treat anemia in patients with chronic kidney diseases (CKD) in PD models. FG-4592 attenuates MPP+ -induced apoptosis and loss of tyrosine hydroxylase (TH) in SH-SY5Y cells. Pretreatment with FG-4592 mitigates MPP+-induced loss of mitochondrial membrane potential (MMP), mitochondrial oxygen consumption rate (OCR), production of reactive oxygen species (ROS) and ATP. Furthermore, FG-4592 counterbalances the oxidative stress through up-regulating nuclear factor erythroid 2 p45-related factor 2 (Nrf-2), heme...Continue Reading

References

Mar 1, 1992·Journal of the Neurological Sciences·M F BealE D Bird
Sep 1, 1991·Journal of Neuroscience Methods·R Drucker-Colín, F García-Hernández
May 1, 1993·Journal of Neuropathology and Experimental Neurology·M S PollanenC Bergeron
May 13, 1997·Proceedings of the National Academy of Sciences of the United States of America·G CohenN Kesler
Aug 28, 1997·Nature·M G SpillantiniM Goedert
Nov 5, 1997·Journal of Neurochemistry·J Haavik
Jun 17, 1998·Molecular Neurobiology·J Haavik, K Toska
Jul 15, 1999·Biochemical and Biophysical Research Communications·V SrinivasJ Caro
Aug 30, 2000·The Journal of Biological Chemistry·F H AganiJ C LaManna
May 21, 2004·Nature Reviews. Neuroscience·Frank R Sharp, Myriam Bernaudin
Jun 2, 2005·Proceedings of the National Academy of Sciences of the United States of America·Zhaohui FengShengkan Jin
Jul 28, 2005·Developmental Neuroscience·Ruiqiong RanFrank R Sharp
Mar 21, 2006·Proceedings of the National Academy of Sciences of the United States of America·Li YuMichael Lenardo
Nov 4, 2008·Nature Clinical Practice. Neurology·Claire Henchcliffe, M Flint Beal
Jul 9, 2009·Physiological Reviews·Gregory R Steinberg, Bruce E Kemp
Oct 12, 2010·Science Translational Medicine·Bin ZhengUNKNOWN Global PD Gene Expression (GPEX) Consortium
Oct 12, 2010·Biochimica Et Biophysica Acta·Richard C Scarpulla
Oct 23, 2010·Molecular Cell·Amar J MajmundarM Celeste Simon
Nov 9, 2010·Biochimica Et Biophysica Acta·Thomas HackenbeckMichael S Wiesener
Mar 8, 2011·Trends in Molecular Medicine·Seth L Masters, Luke A J O'Neill
Apr 7, 2011·The EMBO Journal·Martin Graef, Jodi Nunnari
Jun 21, 2011·Parkinson's Disease·Kyota FujitaMami Noda
Oct 11, 2011·Cellular and Molecular Life Sciences : CMLS·Giuseppa MudòDan Lindholm
Apr 21, 2012·International Journal of Cell Biology·Trond Lamark, Terje Johansen
Jun 26, 2013·Journal of Chemical Information and Modeling·Mahesh Kumar Teli, Rajanikant G K
Aug 16, 2013·Redox Biology·Jianhua Zhang
Nov 12, 2013·Nature Biotechnology·Aaron Bouchie
Mar 12, 2015·Trends in Biochemical Sciences·Brent J RyanRichard Wade-Martins
Aug 5, 2015·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·Anatole BesarabThomas B Neff

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Citations

Dec 17, 2019·American Journal of Physiology. Renal Physiology·Lisa UchidaMasaomi Nangaku
Nov 16, 2019·Cell Death & Disease·Goutham K GanjamCarsten Culmsee
Aug 30, 2020·Neural Regeneration Research·Halimatu Hassan, Ruoli Chen
Dec 3, 2020·Frontiers in Cell and Developmental Biology·Federica CirilloLuigi Anastasia
Feb 16, 2021·Frontiers in Pharmacology·Andrey A PoloznikovIrina G Gazaryan
Jan 13, 2021·International Journal of Molecular Sciences·Johannes BurtscherLuca Zangrandi
Feb 28, 2021·Movement Disorders : Official Journal of the Movement Disorder Society·Johannes BurtscherGrégoire P Millet
Apr 17, 2021·Ageing Research Reviews·Johannes BurtscherGrégoire P Millet
Aug 17, 2021·Frontiers in Cell and Developmental Biology·Elena V MitroshinaMaria V Vedunova
Aug 25, 2021·Neurobiology of Aging·Johannes BurtscherGrégoire P Millet
Aug 28, 2021·Biology·Laura Lestón PinillaLuigi A De Girolamo

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Methods Mentioned

BETA
PCR
flow cytometry
scraping
Protein Assay

Software Mentioned

Image J
GraphPad Prism

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