Endoplasmic reticulum stress-induced caspase-4 activation mediates apoptosis and neurodegeneration in INCL

Human Molecular Genetics
Sung-Jo KimAnil B Mukherjee

Abstract

Infantile neuronal ceroid lipofuscinosis (INCL), a neurodegenerative storage disorder of childhood, is caused by mutations in the palmitoyl-protein thioesterase-1 (PPT1) gene. PPT1 cleaves thioester linkages in S-acylated (palmitoylated) proteins and its mutation causes abnormal intracellular accumulation of fatty-acylated proteins and peptides leading to INCL pathogenesis. Although apoptosis is the suggested cause of neurodegeneration in INCL, the molecular mechanism(s) of apoptosis remains unclear. Using the PPT1-knockout (PPT1-KO) mice that mimic INCL, we previously reported that one mechanism of apoptosis involves endoplasmic reticulum (ER) stress-induced caspase-12 activation. However, the human caspase-12 gene contains several mutations, which make it functionally inactive. Thus, it has been suggested that human caspase-4 is the counterpart of murine caspase-12. Here we report that in the human INCL brain ER stress-induced activation of unfolded protein response (UPR) mediates caspase-4 and caspase-3 activation and apoptosis. Moreover, we show that the INCL brain contains high level of growth-associated protein-43 (GAP-43), which is known to undergo palmitoylation. We also demonstrate that transfection of cultured INCL ce...Continue Reading

References

Jan 1, 1988·American Journal of Medical Genetics. Supplement·J A Rider, D L Rider
Jan 1, 1988·Brain & Development·P Santavuori
Jul 17, 1998·The Journal of Clinical Investigation·A K DasS L Hofmann
Aug 14, 1999·Biochimica Et Biophysica Acta·R E McLaughlin, J B Denny
Apr 25, 2000·Cell·H T Orr, H Y Zoghbi
Aug 31, 2000·Neurobiology of Disease·H C Ha, S H Snyder
Sep 11, 2001·Neurology·K E WisniewskiM Philippart
Nov 22, 2001·Proceedings of the National Academy of Sciences of the United States of America·P GuptaS L Hofmann
Nov 28, 2001·Current Opinion in Neurology·H M Mitchison, S E Mole
Apr 17, 2002·Cell·Alaa El-Din El-HusseiniDavid S Bredt
Jun 11, 2002·Biochemical and Biophysical Research Communications·Heinz FischerErwin Tschachler
Jul 27, 2002·Annual Review of Cell and Developmental Biology·Heather P HardingDavid Ron
Oct 24, 2002·Human Molecular Genetics·Roshni R SingarajaMichael R Hayden
Jan 17, 2003·Journal of Neuropathology and Experimental Neurology·Matti Haltia
Dec 20, 2003·Cell Death and Differentiation·S Oyadomari, M Mori
May 5, 2004·The Journal of Cell Biology·Junichi HitomiMasaya Tohyama
Jul 24, 2004·Nature Medicine·Ella Bossy-WetzelStuart A Lipton
Sep 15, 2004·Developmental Cell·David Ron, Seiichi Oyadomari
Dec 18, 2004·Neuron·Masaki FukataDavid S Bredt
Feb 12, 2005·Science·Oliver RocksPhilippe I H Bastiaens
Jun 15, 2005·Annual Review of Biochemistry·Martin Schröder, Randal J Kaufman

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Citations

Feb 22, 2008·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Changfei LiXuetao Cao
Feb 3, 2009·Apoptosis : an International Journal on Programmed Cell Death·Keita KankiYoshifumi Watanabe
Oct 18, 2011·Apoptosis : an International Journal on Programmed Cell Death·Byeong Mo KimSung Hee Hong
Feb 25, 2009·The Journal of Biological Chemistry·Michael A GitchoNigel J Cairns
Nov 6, 2007·Antioxidants & Redox Signaling·Jyoti D Malhotra, Randal J Kaufman
Dec 17, 2009·Antioxidants & Redox Signaling·Miklós CsalaGábor Bánhegyi
Feb 6, 2009·Human Molecular Genetics·Tamar Farfel-BeckerAnthony H Futerman
Mar 20, 2010·International Journal of Cell Biology·Claudia CerellaLina Ghibelli
Dec 29, 2009·Journal of Neuroinflammation·Antero SalminenJohanna Ojala
Jun 1, 2014·Human Molecular Genetics·Catherine Moorwood, Elisabeth R Barton
Oct 18, 2011·Journal of Inherited Metabolic Disease·Guglielmo R D VillaniPaola Di Natale
Aug 4, 2010·Cellular and Molecular Life Sciences : CMLS·Amanda L Getty, David A Pearce
Dec 24, 2014·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Tomoyuki NishizakiAkito Tanaka
Nov 22, 2011·Biochemical and Biophysical Research Communications·Francesco PezziniAlessandro Simonati
Aug 25, 2010·Cancer Letters·Tom VerfailliePatrizia Agostinis
Feb 24, 2009·Molecular Genetics and Metabolism·Allison M BradburyDouglas R Martin
Mar 24, 2009·Pediatric Neurology·Alessandro SimonatiFilippo M Santorelli
Nov 9, 2007·The Journal of Investigative Dermatology·Yiqun G ShellmanDavid A Norris
Oct 7, 2008·Free Radical Biology & Medicine·Vellareddy AnantharamAnumantha G Kanthasamy
Oct 18, 2015·Journal of Ethnopharmacology·Ching-Fen WuThomas Efferth
Nov 21, 2007·Seminars in Cell & Developmental Biology·Jyoti D Malhotra, Randal J Kaufman
Feb 10, 2007·The FEBS Journal·Hiderou Yoshida
Apr 9, 2013·Environmental Microbiology Reports·Mansha Seth-PasrichaKay D Bidle
Jul 29, 2010·Journal of Biochemical and Molecular Toxicology·Ying-Ying ChenYue-Liang Shen
May 1, 2013·Journal of Cellular Physiology·Kayleen VannuvelThierry Arnould
May 23, 2012·Therapeutic Apheresis and Dialysis : Official Peer-reviewed Journal of the International Society for Apheresis, the Japanese Society for Apheresis, the Japanese Society for Dialysis Therapy·Jianhui ZhouXiangmei Chen

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