Neuroanatomical Quantitative Proteomics Reveals Common Pathogenic Biological Routes between Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Dementia (FTD)

被引:47
|
作者
Oaia Iridoy, Marina [1 ]
Zubiri, Irene [2 ]
Victoria Zelaya, Maria [3 ]
Martinez, Leyre [1 ]
Ausin, Karina [2 ]
Lachen-Montes, Mercedes [2 ,4 ]
Santamaria, Enrique [2 ,4 ]
Fernandez-Irigoyen, Joaquin [2 ,4 ]
Jerico, Ivonne [1 ]
机构
[1] IdiSNA Navarra Inst Hlth Res, ComplejoHosp Navarra CHN, Dept Neurol, Irunlarrea 3, Pamplona 31008, Spain
[2] Univ Publ Navarra UPNA, CHN, IdiSNA, Proteored ISCIII,Prote Unit,Navarrabiomed, Irunlarrea 3, Pamplona 31008, Spain
[3] IdiSNA Navarra Inst Hlth Res, Pathol Anat Serv Complejo Hosp Navarrra CHN, Irunlarrea 3, Pamplona 31008, Spain
[4] IdiSNA, Univ Publ Navarra UPNA, CHN, Clin Neuroprote Grp,Navarrabiomed, Irunlarrea 3, Pamplona 31008, Spain
来源
关键词
amyotrophic lateral sclerosis (ALS); frontotemporal dementia (FTD); motor neuron; proteomics; CEREBROSPINAL-FLUID; LOBAR DEGENERATION; BINDING-PROTEIN; CALCIUM-BINDING; MOTOR-NEURONS; CELL-DEATH; GALECTIN-3; DISEASE; GENE; EXPRESSION;
D O I
10.3390/ijms20010004
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
(1) Background: Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are neurodegenerative disorders with an overlap in clinical presentation and neuropathology. Common and differential mechanisms leading to protein expression changes and neurodegeneration in ALS and FTD were studied trough a deep neuroproteome mapping of the spinal cord. (2) Methods: A liquid chromatography tandem mass spectrometry (LC-MS/MS) analysis of the spinal cord from ALS-TAR DNA-binding protein 43 (TDP-43) subjects, ubiquitin-positive frontotemporal lobar degeneration (FTLD-U) subjects and controls without neurodegenerative disease was performed. (3) Results: 281 differentially expressed proteins were detected among ALS versus controls, while 52 proteins were dysregulated among FTLD-U versus controls. Thirty-three differential proteins were shared between both syndromes. The resulting data was subjected to network-driven proteomics analysis, revealing mitochondrial dysfunction and metabolic impairment, both for ALS and FTLD-U that could be validated through the confirmation of expression levels changes of the Prohibitin (PHB) complex. (4) Conclusions: ALS-TDP-43 and FTLD-U share molecular and functional alterations, although part of the proteostatic impairment is region- and disease-specific. We have confirmed the involvement of specific proteins previously associated with ALS (Galectin 2 (LGALS3), Transthyretin (TTR), Protein S100-A6 (S100A6), and Protein S100-A11 (S100A11)) and have shown the involvement of proteins not previously described in the ALS context (Methanethiol oxidase (SELENBP1), Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN-1), Calcyclin-binding protein (CACYBP) and Rho-associated protein kinase 2 (ROCK2)).
引用
收藏
页数:24
相关论文
共 50 条
  • [31] Is CHCHD10 Pro34Ser pathogenic for frontotemporal dementia and amyotrophic lateral sclerosis?
    Dobson-Stone, Carol
    Shaw, Alex D.
    Hallupp, Marianne
    Bartley, Lauren
    McCann, Heather
    Brooks, William S.
    Loy, Clement T.
    Schofield, Peter R.
    Mather, Karen A.
    Kochan, Nicole A.
    Sachdev, Perminder S.
    Halliday, Glenda M.
    Piguet, Olivier
    Hodges, John R.
    Kwok, John B. J.
    BRAIN, 2015, 138 : E385 - U17
  • [32] Selective Genetic Overlap Between Amyotrophic Lateral Sclerosis and Diseases of the Frontotemporal Dementia Spectrum
    Karch, Celeste M.
    Wen, Natalie
    Fan, Chun C.
    Yokoyama, Jennifer S.
    Kouri, Naomi
    Ross, Owen A.
    Hoeglinger, Gunter
    Mueller, Ulrich
    Ferrari, Raffaele
    Hardy, John
    Schellenberg, Gerard D.
    Sleiman, Patrick M.
    Momeni, Parastoo
    Hess, Christopher P.
    Miller, Bruce L.
    Sharma, Manu
    Van Deerlin, Vivianna
    Smeland, Olav B.
    Andreassen, Ole A.
    Dale, Anders M.
    Desikan, Rahul S.
    JAMA NEUROLOGY, 2018, 75 (07) : 860 - 875
  • [33] The Interplay Between Autophagy and RNA Homeostasis: Implications for Amyotrophic Lateral Sclerosis and Frontotemporal Dementia
    Houghton, O. H.
    Mizielinska, S.
    Gomez-Suaga, P.
    FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY, 2022, 10
  • [34] Amyotrophic lateral sclerosis and frontotemporal dementia-On the way to common gene-specific treatment approaches
    Anderl-Straub, Sarah
    Schuster, Joachim
    Dorst, Johannes
    Ludolph, Albert C.
    NERVENARZT, 2021, 92 (12): : 1219 - 1226
  • [35] Pathogenic Mechanisms and Therapy Development for C9orf72 Amyotrophic Lateral Sclerosis/Frontotemporal Dementia
    Jiang, Jie
    Ravits, John
    NEUROTHERAPEUTICS, 2019, 16 (04) : 1115 - 1132
  • [36] Reply: Is CHCHD10 Pro34Ser pathogenic for frontotemporal dementia and amyotrophic lateral sclerosis?
    Bannwarth, Sylvie
    Ait-El-Mkadem, Samira
    Chaussenot, Annabelle
    Genin, Emmanuelle C.
    Lacas-Gervais, Sandra
    Fragaki, Konstantina
    Berg-Alonso, Laetitia
    Kageyama, Yusuke
    Serre, Valerie
    Moore, David
    Verschueren, Annie
    Rouzier, Cecile
    Le Ber, Isabelle
    Auge, Gaelle
    Cochaud, Charlotte
    Lespinasse, Francoise
    N'Guyen, Karine
    de Septenville, Anne
    Brice, Alexis
    Yu-Wai-Man, Patrick
    Sesaki, Hiromi
    Pouget, Jean
    Paquis-Flucklinger, Veronique
    BRAIN, 2015, 138 : E386 - U20
  • [37] Pathogenic Mechanisms and Therapy Development for C9orf72 Amyotrophic Lateral Sclerosis/Frontotemporal Dementia
    Jie Jiang
    John Ravits
    Neurotherapeutics, 2019, 16 : 1115 - 1132
  • [38] Unbiased Label-Free Quantitative Proteomics of Cells Expressing Amyotrophic Lateral Sclerosis (ALS) Mutations in CCNF Reveals Activation of the Apoptosis Pathway: A Workflow to Screen Pathogenic Gene Mutations
    Cheng, Flora
    De Luca, Alana
    Hogan, Alison L.
    Rayner, Stephanie L.
    Davidson, Jennilee M.
    Watchon, Maxinne
    Stevens, Claire H.
    Munoz, Sonia Sanz
    Ooi, Lezanne
    Yerbury, Justin J.
    Don, Emily K.
    Fifita, Jennifer A.
    Villalva, Maria D.
    Suddull, Hannah
    Chapman, Tyler R.
    Hedl, Thomas J.
    Walker, Adam K.
    Yang, Shu
    Morsch, Marco
    Shi, Bingyang
    Blair, Ian P.
    Laird, Angela S.
    Chung, Roger S.
    Lee, Albert
    FRONTIERS IN MOLECULAR NEUROSCIENCE, 2021, 14
  • [39] Delineating the relationship between amyotrophic lateral sclerosis and frontotemporal dementia: Sequence and structure-based predictions
    Kumar, Vijay
    Islam, Asimul
    Hassan, Md. Imtaiyaz
    Ahmad, Faizan
    BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE, 2016, 1862 (09): : 1742 - 1754
  • [40] CHCHD10 Pro34Ser is not a highly penetrant pathogenic variant for amyotrophic lateral sclerosis and frontotemporal dementia
    Abdelkarim, Samir
    Morgan, Sarah
    Plagnol, Vincent
    Lu, Ching-Hua
    Adamson, Gary
    Howard, Robin
    Malaspina, Andrea
    Orrell, Richard
    Sharma, Nikhil
    Sidle, Katie
    Clarke, Jan
    Fox, Nick C.
    Rossor, Martin N.
    Warren, Jason D.
    Clark, Camilla N.
    Rohrer, Jonathan D.
    Fisher, Elizabeth M. C.
    Mead, Simon
    Pittman, Alan
    Fratta, Pietro
    BRAIN, 2016, 139 : E9 - U13