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)).
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页数:24
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