Evaluation of cyanotoxin L-BMAA effect on α-synuclein and TDP43 proteinopathy
The complex interplay between genetic and environmental factors is considered the cause of neurodegenerative diseases including Parkinson’s disease (PD) and Amyotrophic Lateral Sclerosis (ALS). Among the environmental factors, toxins produced by cyanobacteria have received much attention due to the...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2024-03-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1360068/full |
| _version_ | 1827308834738143232 |
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| author | Paola Sini Grazia Galleri Cristina Ciampelli Manuela Galioto Bachisio Mario Padedda Antonella Lugliè Ciro Iaccarino Claudia Crosio |
| author_facet | Paola Sini Grazia Galleri Cristina Ciampelli Manuela Galioto Bachisio Mario Padedda Antonella Lugliè Ciro Iaccarino Claudia Crosio |
| author_sort | Paola Sini |
| collection | DOAJ |
| description | The complex interplay between genetic and environmental factors is considered the cause of neurodegenerative diseases including Parkinson’s disease (PD) and Amyotrophic Lateral Sclerosis (ALS). Among the environmental factors, toxins produced by cyanobacteria have received much attention due to the significant increase in cyanobacteria growth worldwide. In particular, L-BMAA toxin, produced by diverse taxa of cyanobacteria, dinoflagellates and diatoms, has been extensively correlated to neurodegeneration. The molecular mechanism of L-BMAA neurotoxicity is still cryptic and far from being understood. In this research article, we have investigated the molecular pathways altered by L-BMAA exposure in cell systems, highlighting a significant increase in specific stress pathways and an impairment in autophagic processes. Interestingly, these changes lead to the accumulation of both α-synuclein and TDP43, which are correlated with PD and ALS proteinopathy, respectively. Finally, we were able to demonstrate specific alterations of TDP43 WT or pathological mutants with respect to protein accumulation, aggregation and cytoplasmic translocation, some of the typical features of both sporadic and familial ALS. |
| first_indexed | 2024-04-24T19:17:33Z |
| format | Article |
| id | doaj.art-8538733c908a4f4abddccb162d6c8f1f |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-24T19:17:33Z |
| publishDate | 2024-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-8538733c908a4f4abddccb162d6c8f1f2024-03-26T04:44:48ZengFrontiers Media S.A.Frontiers in Immunology1664-32242024-03-011510.3389/fimmu.2024.13600681360068Evaluation of cyanotoxin L-BMAA effect on α-synuclein and TDP43 proteinopathyPaola Sini0Grazia Galleri1Cristina Ciampelli2Manuela Galioto3Bachisio Mario Padedda4Antonella Lugliè5Ciro Iaccarino6Claudia Crosio7Laboratory of Molecular Biology, Department of Biomedical Sciences, University of Sassari, Sassari, ItalyLaboratory of Molecular Biology, Department of Biomedical Sciences, University of Sassari, Sassari, ItalyLaboratory of Molecular Biology, Department of Biomedical Sciences, University of Sassari, Sassari, ItalyLaboratory of Molecular Biology, Department of Biomedical Sciences, University of Sassari, Sassari, ItalyLaboratory of Ecology, Department of Architecture, Design and Urban Planning, University of Sassari, Sassari, ItalyLaboratory of Ecology, Department of Architecture, Design and Urban Planning, University of Sassari, Sassari, ItalyLaboratory of Molecular Biology, Department of Biomedical Sciences, University of Sassari, Sassari, ItalyLaboratory of Molecular Biology, Department of Biomedical Sciences, University of Sassari, Sassari, ItalyThe complex interplay between genetic and environmental factors is considered the cause of neurodegenerative diseases including Parkinson’s disease (PD) and Amyotrophic Lateral Sclerosis (ALS). Among the environmental factors, toxins produced by cyanobacteria have received much attention due to the significant increase in cyanobacteria growth worldwide. In particular, L-BMAA toxin, produced by diverse taxa of cyanobacteria, dinoflagellates and diatoms, has been extensively correlated to neurodegeneration. The molecular mechanism of L-BMAA neurotoxicity is still cryptic and far from being understood. In this research article, we have investigated the molecular pathways altered by L-BMAA exposure in cell systems, highlighting a significant increase in specific stress pathways and an impairment in autophagic processes. Interestingly, these changes lead to the accumulation of both α-synuclein and TDP43, which are correlated with PD and ALS proteinopathy, respectively. Finally, we were able to demonstrate specific alterations of TDP43 WT or pathological mutants with respect to protein accumulation, aggregation and cytoplasmic translocation, some of the typical features of both sporadic and familial ALS.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1360068/fullL-BMAAcyanotoxinsTDP43α-synucleinALSPD |
| spellingShingle | Paola Sini Grazia Galleri Cristina Ciampelli Manuela Galioto Bachisio Mario Padedda Antonella Lugliè Ciro Iaccarino Claudia Crosio Evaluation of cyanotoxin L-BMAA effect on α-synuclein and TDP43 proteinopathy Frontiers in Immunology L-BMAA cyanotoxins TDP43 α-synuclein ALS PD |
| title | Evaluation of cyanotoxin L-BMAA effect on α-synuclein and TDP43 proteinopathy |
| title_full | Evaluation of cyanotoxin L-BMAA effect on α-synuclein and TDP43 proteinopathy |
| title_fullStr | Evaluation of cyanotoxin L-BMAA effect on α-synuclein and TDP43 proteinopathy |
| title_full_unstemmed | Evaluation of cyanotoxin L-BMAA effect on α-synuclein and TDP43 proteinopathy |
| title_short | Evaluation of cyanotoxin L-BMAA effect on α-synuclein and TDP43 proteinopathy |
| title_sort | evaluation of cyanotoxin l bmaa effect on α synuclein and tdp43 proteinopathy |
| topic | L-BMAA cyanotoxins TDP43 α-synuclein ALS PD |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1360068/full |
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