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piRNA/PIWI Protein Complex as a Potential Biomarker in Sporadic Amyotrophic Lateral Sclerosis
The pathological hallmark of the majority of amyotrophic lateral sclerosis (ALS) cases is the mislocalization and aggregation of TAR DNA-binding protein 43 (TDP-43), an RNA-binding protein. Several studies have attributed disease processes of ALS to abnormal RNA metabolism. However, dysregulated bio...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer US
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8882100/ https://www.ncbi.nlm.nih.gov/pubmed/35015250 http://dx.doi.org/10.1007/s12035-021-02686-2 |
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author | Abdelhamid, Rehab F. Ogawa, Kotaro Beck, Goichi Ikenaka, Kensuke Takeuchi, Eriko Yasumizu, Yoshiaki Jinno, Jyunki Kimura, Yasuyoshi Baba, Kousuke Nagai, Yoshitaka Okada, Yukinori Saito, Yuko Murayama, Shigeo Mochizuki, Hideki Nagano, Seiichi |
author_facet | Abdelhamid, Rehab F. Ogawa, Kotaro Beck, Goichi Ikenaka, Kensuke Takeuchi, Eriko Yasumizu, Yoshiaki Jinno, Jyunki Kimura, Yasuyoshi Baba, Kousuke Nagai, Yoshitaka Okada, Yukinori Saito, Yuko Murayama, Shigeo Mochizuki, Hideki Nagano, Seiichi |
author_sort | Abdelhamid, Rehab F. |
collection | PubMed |
description | The pathological hallmark of the majority of amyotrophic lateral sclerosis (ALS) cases is the mislocalization and aggregation of TAR DNA-binding protein 43 (TDP-43), an RNA-binding protein. Several studies have attributed disease processes of ALS to abnormal RNA metabolism. However, dysregulated biogenesis of RNA, especially non-coding RNA (ncRNA), is poorly understood. To resolve it, RNA-Seq, biochemical, and immunohistochemical analyses were performed on the pyramidal tract of the medulla oblongata of sporadic ALS (sALS) and control postmortem brain samples. Here, we report perturbation of ncRNA biogenesis in PIWI-interacting RNA (piRNA) in several sALS brain samples associated with TDP-43 pathology. In addition, we confirmed the dysregulation of two PIWI homologs, PIWI-like-mediated gene silencing 1 (PIWIL1) and PIWIL4, which bind to piRNAs to regulate their expression. PIWIL1 was mislocalized and co-localized with TDP-43 in motor neurons of sporadic ALS lumbar cords. Our results imply that dysregulation of piRNA, PIWIL1, and PIWIL4 is linked to pathogenesis of ALS. Based on these results, piRNAs and PIWI proteins are potential diagnostic biomarkers and therapeutic targets of ALS. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12035-021-02686-2. |
format | Online Article Text |
id | pubmed-8882100 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Springer US |
record_format | MEDLINE/PubMed |
spelling | pubmed-88821002022-03-02 piRNA/PIWI Protein Complex as a Potential Biomarker in Sporadic Amyotrophic Lateral Sclerosis Abdelhamid, Rehab F. Ogawa, Kotaro Beck, Goichi Ikenaka, Kensuke Takeuchi, Eriko Yasumizu, Yoshiaki Jinno, Jyunki Kimura, Yasuyoshi Baba, Kousuke Nagai, Yoshitaka Okada, Yukinori Saito, Yuko Murayama, Shigeo Mochizuki, Hideki Nagano, Seiichi Mol Neurobiol Article The pathological hallmark of the majority of amyotrophic lateral sclerosis (ALS) cases is the mislocalization and aggregation of TAR DNA-binding protein 43 (TDP-43), an RNA-binding protein. Several studies have attributed disease processes of ALS to abnormal RNA metabolism. However, dysregulated biogenesis of RNA, especially non-coding RNA (ncRNA), is poorly understood. To resolve it, RNA-Seq, biochemical, and immunohistochemical analyses were performed on the pyramidal tract of the medulla oblongata of sporadic ALS (sALS) and control postmortem brain samples. Here, we report perturbation of ncRNA biogenesis in PIWI-interacting RNA (piRNA) in several sALS brain samples associated with TDP-43 pathology. In addition, we confirmed the dysregulation of two PIWI homologs, PIWI-like-mediated gene silencing 1 (PIWIL1) and PIWIL4, which bind to piRNAs to regulate their expression. PIWIL1 was mislocalized and co-localized with TDP-43 in motor neurons of sporadic ALS lumbar cords. Our results imply that dysregulation of piRNA, PIWIL1, and PIWIL4 is linked to pathogenesis of ALS. Based on these results, piRNAs and PIWI proteins are potential diagnostic biomarkers and therapeutic targets of ALS. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12035-021-02686-2. Springer US 2022-01-11 2022 /pmc/articles/PMC8882100/ /pubmed/35015250 http://dx.doi.org/10.1007/s12035-021-02686-2 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Abdelhamid, Rehab F. Ogawa, Kotaro Beck, Goichi Ikenaka, Kensuke Takeuchi, Eriko Yasumizu, Yoshiaki Jinno, Jyunki Kimura, Yasuyoshi Baba, Kousuke Nagai, Yoshitaka Okada, Yukinori Saito, Yuko Murayama, Shigeo Mochizuki, Hideki Nagano, Seiichi piRNA/PIWI Protein Complex as a Potential Biomarker in Sporadic Amyotrophic Lateral Sclerosis |
title | piRNA/PIWI Protein Complex as a Potential Biomarker in Sporadic Amyotrophic Lateral Sclerosis |
title_full | piRNA/PIWI Protein Complex as a Potential Biomarker in Sporadic Amyotrophic Lateral Sclerosis |
title_fullStr | piRNA/PIWI Protein Complex as a Potential Biomarker in Sporadic Amyotrophic Lateral Sclerosis |
title_full_unstemmed | piRNA/PIWI Protein Complex as a Potential Biomarker in Sporadic Amyotrophic Lateral Sclerosis |
title_short | piRNA/PIWI Protein Complex as a Potential Biomarker in Sporadic Amyotrophic Lateral Sclerosis |
title_sort | pirna/piwi protein complex as a potential biomarker in sporadic amyotrophic lateral sclerosis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8882100/ https://www.ncbi.nlm.nih.gov/pubmed/35015250 http://dx.doi.org/10.1007/s12035-021-02686-2 |
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