دورية أكاديمية
أعرض في EDS

Serpin neuropathology in the P497S UBQLN2 mouse model of ALS/FTD.

التفاصيل البيبلوغرافية
العنوان: Serpin neuropathology in the P497S UBQLN2 mouse model of ALS/FTD.
المؤلفون: Higgins NR; Program in Molecular Medicine, University of Maryland School of Medicine, Baltimore, MD, USA.; Center for Biomedical Engineering and Technology, Department of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, MD, USA., Greenslade JE; Center for Biomedical Engineering and Technology, Department of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, MD, USA., Wu JJ; Center for Biomedical Engineering and Technology, Department of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, MD, USA., Miranda E; Department of Biology and Biotechnologies 'Charles Darwin', Pasteur Institute - Cenci Bolognetti Foundation, Sapienza University of Rome, Rome, Italy., Galliciotti G; Institute of Neuropathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Monteiro MJ; Program in Molecular Medicine, University of Maryland School of Medicine, Baltimore, MD, USA.; Center for Biomedical Engineering and Technology, Department of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, MD, USA.
المصدر: Brain pathology (Zurich, Switzerland) [Brain Pathol] 2021 Sep; Vol. 31 (5), pp. e12948. Date of Electronic Publication: 2021 Mar 29.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: International Society of Neuropathology Country of Publication: Switzerland NLM ID: 9216781 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1750-3639 (Electronic) Linking ISSN: 10156305 NLM ISO Abbreviation: Brain Pathol Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Zürich, Switzerland : International Society of Neuropathology, [1990-
مواضيع طبية MeSH: Adaptor Proteins, Signal Transducing/*metabolism , Amyotrophic Lateral Sclerosis/*genetics , Amyotrophic Lateral Sclerosis/*pathology , Autophagy-Related Proteins/*metabolism , Frontotemporal Dementia/*pathology , Serpins/*genetics, Adaptor Proteins, Signal Transducing/genetics ; Amyotrophic Lateral Sclerosis/metabolism ; Animals ; Autophagy-Related Proteins/genetics ; Disease Models, Animal ; Frontotemporal Dementia/genetics ; Frontotemporal Dementia/metabolism ; Mice, Inbred C57BL ; Mice, Transgenic ; Motor Neurons/metabolism ; Motor Neurons/pathology ; Serpins/metabolism ; Spinal Cord/pathology ; Mice
مستخلص: Accumulating evidence suggests X-linked dominant mutations in UBQLN2 cause amyotrophic lateral sclerosis (ALS) with frontotemporal dementia (FTD) through both loss- and gain-of-function mechanisms. However, the mechanisms by which the mutations cause disease are still unclear. The goal of the study was to uncover the possible pathomechanism(s) by which UBQLN2 mutations cause ALS/FTD. An analysis of proteomic changes in neuronal tissue was used to identify proteins with altered accumulation in the P497S UBQLN2 transgenic mouse model of ALS/FTD. We then used immunocytochemistry and biochemical techniques to confirm protein changes in the mutant P497S mice. Additionally, we used cell lines inactivated of UBQLN2 expression to determine whether its loss underlies the alteration in the proteins seen in P497S mice. The proteome screen identified a dramatic alteration of serine protease inhibitor (serpin) proteins in the mutant P497S animals. Double immunofluorescent staining of brain and spinal cord tissues of the mutant and control mice revealed an age-dependent change in accumulation of Serpin A1, C1, and I1 in puncta whose staining colocalized with UBQLN2 puncta in the mutant P497S mice. Serpin A1 aggregation in P497S animals was confirmed by biochemical extraction and filter retardation assays. A similar phenomenon of serpin protein aggregation was found in HeLa and NSC34 motor neuron cells with inactivated UBQLN2 expression. We found aberrant aggregation of serpin proteins, particularly Serpin A1, in the brain and spinal cord of the P497S UBQLN2 mouse model of ALS/FTD. Similar aggregation of serpin proteins was found in UBQLN2 knockout cells suggesting that serpin aggregation in the mutant P497S animals may stem from loss of UBQLN2 function. Because serpin aggregation is known to cause disease through both loss- and gain-of-function mechanisms, we speculate that their accumulation in the P497S mouse model of ALS/FTD may contribute to disease pathogenesis through similar mechanism(s).
(© 2021 The Authors. Brain Pathology published by John Wiley & Sons Ltd on behalf of International Society of Neuropathology.)
References: Skelet Muscle. 2017 Jun 1;7(1):10. (PMID: 28571586)
Nat Struct Biol. 1995 May;2(5):363-7. (PMID: 7664092)
Lancet. 2017 Nov 4;390(10107):2084-2098. (PMID: 28552366)
Proc Am Thorac Soc. 2010 Nov;7(6):363-7. (PMID: 21030514)
J Neurosci. 1994 Mar;14(3 Pt 2):1820-33. (PMID: 8126574)
J Biol Chem. 2011 Jun 10;286(23):20835-44. (PMID: 21507957)
Nature. 2016 Nov 10;539(7628):197-206. (PMID: 27830784)
J Biol Chem. 1996 Mar 15;271(11):6523-9. (PMID: 8626456)
J Hepatol. 2016 Aug;65(2):413-24. (PMID: 27034252)
Nature. 2011 Aug 21;477(7363):211-5. (PMID: 21857683)
Neurology. 2007 Oct 16;69(16):1569-79. (PMID: 17761554)
Acta Neuropathol. 2019 May;137(5):715-730. (PMID: 30465257)
Int J Biochem Cell Biol. 2008;40(6-7):1273-86. (PMID: 18289918)
Proc Natl Acad Sci U S A. 2016 Nov 22;113(47):E7580-E7589. (PMID: 27834214)
Nat Rev Genet. 2002 Oct;3(10):759-68. (PMID: 12360234)
J Biol Chem. 1996 Sep 13;271(37):22791-5. (PMID: 8798455)
PLoS One. 2015 Jun 15;10(6):e0130162. (PMID: 26075709)
Hum Genomics. 2013 Oct 30;7:22. (PMID: 24172014)
Nat Med. 2020 Jan;26(1):131-142. (PMID: 31932797)
J Biol Chem. 2006 Feb 17;281(7):4467-76. (PMID: 16365039)
J Cell Biol. 2009 Oct 19;187(2):201-17. (PMID: 19822669)
J Neurol Sci. 1998 Oct;160 Suppl 1:S73-9. (PMID: 9851654)
Prion. 2007 Jan-Mar;1(1):15-20. (PMID: 19164889)
Expert Rev Mol Med. 2006 Dec 11;8(31):1-19. (PMID: 17156576)
N Engl J Med. 2017 Jul 13;377(2):162-172. (PMID: 28700839)
J Biol Chem. 1992 Jan 15;267(2):1072-80. (PMID: 1530934)
Am J Pathol. 2006 Oct;169(4):1343-52. (PMID: 17003490)
J Biol Chem. 2009 Aug 21;284(34):22793-802. (PMID: 19549782)
Proc Natl Acad Sci U S A. 2016 Jun 7;113(23):6484-9. (PMID: 27222580)
J Cell Biol. 2019 Oct 7;218(10):3171-3187. (PMID: 31537714)
Science. 2020 Apr 24;368(6489):. (PMID: 32327570)
J Neurochem. 2014 Apr;129(1):99-106. (PMID: 24215460)
Cell. 1988 Feb 26;52(4):487-501. (PMID: 3257719)
J Thromb Haemost. 2011 Jul;9 Suppl 1:26-34. (PMID: 21781239)
Nat Cell Biol. 2011 Mar;13(3):184-90. (PMID: 21364565)
Brain Res Mol Brain Res. 1998 May;56(1-2):99-107. (PMID: 9602079)
Cell Mol Life Sci. 2020 Oct;77(19):3859-3873. (PMID: 31802140)
Lancet. 2015 Oct 24;386(10004):1672-82. (PMID: 26595641)
Front Neurosci. 2019 Dec 06;13:1310. (PMID: 31866818)
Biochem J. 2016 Aug 1;473(15):2273-93. (PMID: 27470592)
Nat Rev Drug Discov. 2012 Jan 03;11(1):69-86. (PMID: 22212680)
Nature. 2016 Jan 21;529(7586):326-35. (PMID: 26791723)
J Biol Chem. 1995 Jul 14;270(28):16864-70. (PMID: 7622502)
Adv Exp Med Biol. 2008;632:71-9. (PMID: 19025115)
J Biol Chem. 2021 Jan-Jun;296:100153. (PMID: 33277362)
PLoS One. 2015 Jun 17;10(6):e0130136. (PMID: 26083412)
Proteins. 1995 Jul;22(3):210-25. (PMID: 7479695)
Trends Genet. 2018 Jun;34(6):404-423. (PMID: 29605155)
Prion. 2009 Jan-Mar;3(1):12-4. (PMID: 19372754)
Physiol Rev. 2011 Apr;91(2):461-553. (PMID: 21527731)
J Neuroinflammation. 2016 Jun 01;13(1):131. (PMID: 27245439)
Nature. 2000 Apr 13;404(6779):770-4. (PMID: 10783891)
Acta Neuropathol. 2017 Nov;134(5):715-728. (PMID: 28808785)
J Biol Chem. 2004 Jul 2;279(27):28283-91. (PMID: 15090543)
Eur Respir J. 2016 Mar;47(3):1005-9. (PMID: 26846838)
Nature. 2020 Dec;588(7838):459-465. (PMID: 32866962)
Annu Rev Biochem. 2009;78:147-76. (PMID: 19245336)
JCI Insight. 2018 Oct 4;3(19):. (PMID: 30282815)
Neurobiol Aging. 2014 Oct;35(10):2394-403. (PMID: 24795221)
Acta Neuropathol Commun. 2020 Oct 7;8(1):164. (PMID: 33028421)
Cell. 1997 Aug 8;90(3):549-58. (PMID: 9267034)
Structure. 2019 Jun 4;27(6):879-881. (PMID: 31167121)
Nature. 1982 Jul 22;298(5872):329-34. (PMID: 7045697)
Sci Rep. 2016 May 31;6:24708. (PMID: 27241590)
Genome Biol. 2006;7(5):216. (PMID: 16737556)
Biochim Biophys Acta. 2013 Dec;1833(12):3460-3470. (PMID: 23850759)
J Infect Dis. 2011 Aug 15;204(4):592-600. (PMID: 21791661)
Nature. 1999 Sep 23;401(6751):376-9. (PMID: 10517635)
Biochem J. 2020 Sep 30;477(18):3471-3497. (PMID: 32965492)
Genomics. 2006 Aug;88(2):173-84. (PMID: 16713170)
Curr Opin Neurol. 2018 Oct;31(5):635-639. (PMID: 30048339)
Int J Mol Sci. 2017 Aug 28;18(9):. (PMID: 28846632)
Acta Neuropathol Commun. 2019 Jul 18;7(1):103. (PMID: 31319884)
Am J Physiol Lung Cell Mol Physiol. 2006 Oct;291(4):L619-27. (PMID: 16617093)
Am J Med. 1988 Jun 24;84(6A):13-31. (PMID: 3289385)
Nature. 2003 Dec 18;426(6968):895-9. (PMID: 14685250)
PLoS Genet. 2019 Mar 14;15(3):e1007948. (PMID: 30870413)
Chem Rev. 2002 Dec;102(12):4751-804. (PMID: 12475206)
Trends Biochem Sci. 2006 Aug;31(8):427-35. (PMID: 16820297)
J Biol Chem. 2009 Jul 3;284(27):18202-9. (PMID: 19423713)
Science. 2006 Oct 6;314(5796):130-3. (PMID: 17023659)
Proc Natl Acad Sci U S A. 2020 Jun 30;117(26):15230-15241. (PMID: 32513711)
Ann Clin Transl Neurol. 2020 Feb;7(2):191-199. (PMID: 31957347)
PLoS One. 2012;7(9):e44401. (PMID: 22970211)
Exp Cell Res. 1996 Mar 15;223(2):443-51. (PMID: 8601422)
معلومات مُعتمدة: R01 NS098243 United States NS NINDS NIH HHS; R01 NS100008 United States NS NINDS NIH HHS; RF1 NS098243 United States NS NINDS NIH HHS
فهرسة مساهمة: Keywords: Ubiquilin-2 (UBQLN2); amyotrophic lateral sclerosis (ALS); frontotemporal dementia (FTD); protein aggregation; serpin
المشرفين على المادة: 0 (Adaptor Proteins, Signal Transducing)
0 (Autophagy-Related Proteins)
0 (Serpins)
0 (UBQLN2 protein, mouse)
SCR Disease Name: Frontotemporal Dementia With Motor Neuron Disease
تواريخ الأحداث: Date Created: 20210329 Date Completed: 20220203 Latest Revision: 20240226
رمز التحديث: 20240226
مُعرف محوري في PubMed: PMC8387369
DOI: 10.1111/bpa.12948
PMID: 33780087
قاعدة البيانات: MEDLINE
الوصف
تدمد:1750-3639
DOI:10.1111/bpa.12948