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Matveeva, A., Watters, O., Rukhadze, A., Khemka, N., Gentile, D., Perez, I.F., Llorente-Folch, I., Farrell, C., Lo Cacciato, E., Jackson, J., Piazzesi, A., Wischhof, L., Woods, I., Halang, L., Hogg, M. 
ORCID: 0000-0002-2815-8761, Muñoz, A.G., Dillon, E.T., Matallanas, D., Arijs, I., Lambrechts, D., Bano, D., Connolly, N.M.C. and Prehn, J.H.M.,
2023.
Integrated analysis of transcriptomic and proteomic alterations in mouse models of ALS/FTD identify early metabolic adaptions with similarities to mitochondrial dysfunction disorders.
Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration.
ISSN 2167-8421
Abstract
Objective: Sporadic and familial amyotrophic lateral sclerosis (ALS) is a fatal progressive neurodegenerative disease that results in loss of motor neurons and, in some patients, associates with frontotemporal dementia (FTD). Apart from the accumulation of proteinaceous deposits, emerging literature indicates that aberrant mitochondrial bioenergetics may contribute to the onset and progression of ALS/FTD. Here we sought to investigate the pathophysiological signatures of mitochondrial dysfunction associated with ALS/FTD.
Methods: By means of label-free mass spectrometry (MS) and mRNA sequencing (mRNA-seq), we report pre-symptomatic changes in the cortices of TDP-43 and FUS mutant mouse models. Using tissues from transgenic mouse models of mitochondrial diseases as a reference, we performed comparative analyses and extracted unique and common mitochondrial signatures that revealed neuroprotective compensatory mechanisms in response to early damage.
Results: In this regard, upregulation of both Acyl-CoA Synthetase Long-Chain Family Member 3 (ACSL3) and mitochondrial tyrosyl-tRNA synthetase 2 (YARS2) were the most representative change in pre-symptomatic ALS/FTD tissues, suggesting that fatty acid beta-oxidation and mitochondrial protein translation are mechanisms of adaptation in response to ALS/FTD pathology.
Conclusions: Together, our unbiased integrative analyses unveil novel molecular components that may influence mitochondrial homeostasis in the earliest phase of ALS.
| Item Type: | Journal article | ||||||
|---|---|---|---|---|---|---|---|
| Publication Title: | Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration | ||||||
| Creators: | Matveeva, A., Watters, O., Rukhadze, A., Khemka, N., Gentile, D., Perez, I.F., Llorente-Folch, I., Farrell, C., Lo Cacciato, E., Jackson, J., Piazzesi, A., Wischhof, L., Woods, I., Halang, L., Hogg, M., Muñoz, A.G., Dillon, E.T., Matallanas, D., Arijs, I., Lambrechts, D., Bano, D., Connolly, N.M.C. and Prehn, J.H.M. | ||||||
| Publisher: | Taylor and Francis | ||||||
| Date: | 1 October 2023 | ||||||
| ISSN: | 2167-8421 | ||||||
| Identifiers: |
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| Rights: | This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/),which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The terms on which this article has been published allow the posting of the Accepted Manuscript in a repository by the author(s) or with their consent. | ||||||
| Divisions: | Schools > School of Science and Technology | ||||||
| Record created by: | Jonathan Gallacher | ||||||
| Date Added: | 05 Oct 2023 16:07 | ||||||
| Last Modified: | 05 Oct 2023 16:07 | ||||||
| URI: | https://irep.ntu.ac.uk/id/eprint/49864 |
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