TDP-43 Proteinopathy and Tauopathy: Do They Have Pathomechanistic Links?
Transactivation response DNA binding protein 43 kDa (TDP-43) and tau are major pathological proteins of neurodegenerative disorders, of which neuronal and glial aggregates are pathological hallmarks. Interestingly, accumulating evidence from neuropathological studies has shown that comorbid TDP-43 p...
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| Format: | Article |
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MDPI AG
2022-12-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/24/15755 |
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| author | Yuichi Riku Mari Yoshida Yasushi Iwasaki Gen Sobue Masahisa Katsuno Shinsuke Ishigaki |
| author_facet | Yuichi Riku Mari Yoshida Yasushi Iwasaki Gen Sobue Masahisa Katsuno Shinsuke Ishigaki |
| author_sort | Yuichi Riku |
| collection | DOAJ |
| description | Transactivation response DNA binding protein 43 kDa (TDP-43) and tau are major pathological proteins of neurodegenerative disorders, of which neuronal and glial aggregates are pathological hallmarks. Interestingly, accumulating evidence from neuropathological studies has shown that comorbid TDP-43 pathology is observed in a subset of patients with tauopathies, and vice versa. The concomitant pathology often spreads in a disease-specific manner and has morphological characteristics in each primary disorder. The findings from translational studies have suggested that comorbid TDP-43 or tau pathology has clinical impacts and that the comorbid pathology is not a bystander, but a part of the disease process. Shared genetic risk factors or molecular abnormalities between TDP-43 proteinopathies and tauopathies, and direct interactions between TDP-43 and tau aggregates, have been reported. Further investigations to clarify the pathogenetic factors that are shared by a broad spectrum of neurodegenerative disorders will establish key therapeutic targets. |
| first_indexed | 2024-03-09T16:19:41Z |
| format | Article |
| id | doaj.art-646be72cc8d44527947964bd37d06388 |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T16:19:41Z |
| publishDate | 2022-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-646be72cc8d44527947964bd37d063882023-11-24T15:27:24ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-12-0123241575510.3390/ijms232415755TDP-43 Proteinopathy and Tauopathy: Do They Have Pathomechanistic Links?Yuichi Riku0Mari Yoshida1Yasushi Iwasaki2Gen Sobue3Masahisa Katsuno4Shinsuke Ishigaki5Institute for Medical Science of Aging, Aichi Medical University, Nagakute 480-1195, JapanInstitute for Medical Science of Aging, Aichi Medical University, Nagakute 480-1195, JapanInstitute for Medical Science of Aging, Aichi Medical University, Nagakute 480-1195, JapanGraduate School of Medicine, Aichi Medical University, Nagakute 480-1195, JapanDepartment of Neurology, Nagoya University Graduate School of Medicine, Nagoya 744-8550, JapanMolecular Neuroscience Research Center, Shiga University of Medical Science, Otsu 520-2192, JapanTransactivation response DNA binding protein 43 kDa (TDP-43) and tau are major pathological proteins of neurodegenerative disorders, of which neuronal and glial aggregates are pathological hallmarks. Interestingly, accumulating evidence from neuropathological studies has shown that comorbid TDP-43 pathology is observed in a subset of patients with tauopathies, and vice versa. The concomitant pathology often spreads in a disease-specific manner and has morphological characteristics in each primary disorder. The findings from translational studies have suggested that comorbid TDP-43 or tau pathology has clinical impacts and that the comorbid pathology is not a bystander, but a part of the disease process. Shared genetic risk factors or molecular abnormalities between TDP-43 proteinopathies and tauopathies, and direct interactions between TDP-43 and tau aggregates, have been reported. Further investigations to clarify the pathogenetic factors that are shared by a broad spectrum of neurodegenerative disorders will establish key therapeutic targets.https://www.mdpi.com/1422-0067/23/24/15755ADALSCBDFTLDLATEPART |
| spellingShingle | Yuichi Riku Mari Yoshida Yasushi Iwasaki Gen Sobue Masahisa Katsuno Shinsuke Ishigaki TDP-43 Proteinopathy and Tauopathy: Do They Have Pathomechanistic Links? International Journal of Molecular Sciences AD ALS CBD FTLD LATE PART |
| title | TDP-43 Proteinopathy and Tauopathy: Do They Have Pathomechanistic Links? |
| title_full | TDP-43 Proteinopathy and Tauopathy: Do They Have Pathomechanistic Links? |
| title_fullStr | TDP-43 Proteinopathy and Tauopathy: Do They Have Pathomechanistic Links? |
| title_full_unstemmed | TDP-43 Proteinopathy and Tauopathy: Do They Have Pathomechanistic Links? |
| title_short | TDP-43 Proteinopathy and Tauopathy: Do They Have Pathomechanistic Links? |
| title_sort | tdp 43 proteinopathy and tauopathy do they have pathomechanistic links |
| topic | AD ALS CBD FTLD LATE PART |
| url | https://www.mdpi.com/1422-0067/23/24/15755 |
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