Metals in ALS TDP-43 Pathology
Amyotrophic lateral sclerosis (ALS), Alzheimer’s disease, Parkinson’s disease and similar neurodegenerative disorders take their toll on patients, caregivers and society. A common denominator for these disorders is the accumulation of aggregated proteins in nerve cells, yet the triggers for these ag...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-11-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/22/12193 |
| _version_ | 1797510093792608256 |
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| author | Lassi Koski Cecilia Ronnevi Elina Berntsson Sebastian K. T. S. Wärmländer Per M. Roos |
| author_facet | Lassi Koski Cecilia Ronnevi Elina Berntsson Sebastian K. T. S. Wärmländer Per M. Roos |
| author_sort | Lassi Koski |
| collection | DOAJ |
| description | Amyotrophic lateral sclerosis (ALS), Alzheimer’s disease, Parkinson’s disease and similar neurodegenerative disorders take their toll on patients, caregivers and society. A common denominator for these disorders is the accumulation of aggregated proteins in nerve cells, yet the triggers for these aggregation processes are currently unknown. In ALS, protein aggregation has been described for the SOD1, C9orf72, FUS and TDP-43 proteins. The latter is a nuclear protein normally binding to both DNA and RNA, contributing to gene expression and mRNA life cycle regulation. TDP-43 seems to have a specific role in ALS pathogenesis, and ubiquitinated and hyperphosphorylated cytoplasmic inclusions of aggregated TDP-43 are present in nerve cells in almost all sporadic ALS cases. ALS pathology appears to include metal imbalances, and environmental metal exposure is a known risk factor in ALS. However, studies on metal-to-TDP-43 interactions are scarce, even though this protein seems to have the capacity to bind to metals. This review discusses the possible role of metals in TDP-43 aggregation, with respect to ALS pathology. |
| first_indexed | 2024-03-10T05:26:51Z |
| format | Article |
| id | doaj.art-b34c068f4f6f42bf92d1c0a0cf70c15e |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T05:26:51Z |
| publishDate | 2021-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-b34c068f4f6f42bf92d1c0a0cf70c15e2023-11-22T23:38:30ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-11-0122221219310.3390/ijms222212193Metals in ALS TDP-43 PathologyLassi Koski0Cecilia Ronnevi1Elina Berntsson2Sebastian K. T. S. Wärmländer3Per M. Roos4Institute of Environmental Medicine, Karolinska Institutet, 171 77 Stockholm, SwedenCapio St. Göran Hospital, 112 19 Stockholm, SwedenDepartment of Biochemistry and Biophysics, Stockholm University, 106 91 Stockholm, SwedenDepartment of Biochemistry and Biophysics, Stockholm University, 106 91 Stockholm, SwedenInstitute of Environmental Medicine, Karolinska Institutet, 171 77 Stockholm, SwedenAmyotrophic lateral sclerosis (ALS), Alzheimer’s disease, Parkinson’s disease and similar neurodegenerative disorders take their toll on patients, caregivers and society. A common denominator for these disorders is the accumulation of aggregated proteins in nerve cells, yet the triggers for these aggregation processes are currently unknown. In ALS, protein aggregation has been described for the SOD1, C9orf72, FUS and TDP-43 proteins. The latter is a nuclear protein normally binding to both DNA and RNA, contributing to gene expression and mRNA life cycle regulation. TDP-43 seems to have a specific role in ALS pathogenesis, and ubiquitinated and hyperphosphorylated cytoplasmic inclusions of aggregated TDP-43 are present in nerve cells in almost all sporadic ALS cases. ALS pathology appears to include metal imbalances, and environmental metal exposure is a known risk factor in ALS. However, studies on metal-to-TDP-43 interactions are scarce, even though this protein seems to have the capacity to bind to metals. This review discusses the possible role of metals in TDP-43 aggregation, with respect to ALS pathology.https://www.mdpi.com/1422-0067/22/22/12193neurodegenerationproteinopathymetallopathyprotein aggregationamyloidmetal exposure |
| spellingShingle | Lassi Koski Cecilia Ronnevi Elina Berntsson Sebastian K. T. S. Wärmländer Per M. Roos Metals in ALS TDP-43 Pathology International Journal of Molecular Sciences neurodegeneration proteinopathy metallopathy protein aggregation amyloid metal exposure |
| title | Metals in ALS TDP-43 Pathology |
| title_full | Metals in ALS TDP-43 Pathology |
| title_fullStr | Metals in ALS TDP-43 Pathology |
| title_full_unstemmed | Metals in ALS TDP-43 Pathology |
| title_short | Metals in ALS TDP-43 Pathology |
| title_sort | metals in als tdp 43 pathology |
| topic | neurodegeneration proteinopathy metallopathy protein aggregation amyloid metal exposure |
| url | https://www.mdpi.com/1422-0067/22/22/12193 |
| work_keys_str_mv | AT lassikoski metalsinalstdp43pathology AT ceciliaronnevi metalsinalstdp43pathology AT elinaberntsson metalsinalstdp43pathology AT sebastianktswarmlander metalsinalstdp43pathology AT permroos metalsinalstdp43pathology |