Environmental insults: critical triggers for amyotrophic lateral sclerosis
Abstract Background Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterised by a rapid loss of lower and upper motor neurons. As a complex disease, the ageing process and complicated gene-environment interactions are involved in the majority of cases. Main body Signifi...
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| Format: | Article |
| Language: | English |
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BMC
2017-06-01
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| Series: | Translational Neurodegeneration |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s40035-017-0087-3 |
| _version_ | 1818954384045768704 |
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| author | Bing Yu Roger Pamphlett |
| author_facet | Bing Yu Roger Pamphlett |
| author_sort | Bing Yu |
| collection | DOAJ |
| description | Abstract Background Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterised by a rapid loss of lower and upper motor neurons. As a complex disease, the ageing process and complicated gene-environment interactions are involved in the majority of cases. Main body Significant advances have been made in unravelling the genetic susceptibility to ALS with massively parallel sequencing technologies, while environmental insults remain a suspected but largely unexplored source of risk. Several studies applying the strategy of Mendelian randomisation have strengthened the link between environmental insults and ALS, but none so far has proved conclusive. We propose a new ALS model which links the current knowledge of genetic factors, ageing and environmental insults. This model provides a mechanism as to how ALS is initiated, with environmental insults playing a critical role. Conclusion The available evidence has suggested that inherited defect(s) could cause mitochondrial dysfunction, which would establish the primary susceptibility to ALS. Further study of the underlying mechanism may shed light on ALS pathogenesis. Environmental insults are a critical trigger for ALS, particularly in the aged individuals with other toxicant susceptible genes. The identification of ALS triggers could lead to preventive strategies for those individuals at risk. |
| first_indexed | 2024-12-20T10:21:18Z |
| format | Article |
| id | doaj.art-9df7fa7005d84516af6f4cd0b8d82f58 |
| institution | Directory Open Access Journal |
| issn | 2047-9158 |
| language | English |
| last_indexed | 2024-12-20T10:21:18Z |
| publishDate | 2017-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Translational Neurodegeneration |
| spelling | doaj.art-9df7fa7005d84516af6f4cd0b8d82f582022-12-21T19:43:55ZengBMCTranslational Neurodegeneration2047-91582017-06-016111010.1186/s40035-017-0087-3Environmental insults: critical triggers for amyotrophic lateral sclerosisBing Yu0Roger Pamphlett1Sydney Medical School (Central), The University of SydneyDiscipline of Pathology, Brain and Mind Centre, The University of SydneyAbstract Background Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterised by a rapid loss of lower and upper motor neurons. As a complex disease, the ageing process and complicated gene-environment interactions are involved in the majority of cases. Main body Significant advances have been made in unravelling the genetic susceptibility to ALS with massively parallel sequencing technologies, while environmental insults remain a suspected but largely unexplored source of risk. Several studies applying the strategy of Mendelian randomisation have strengthened the link between environmental insults and ALS, but none so far has proved conclusive. We propose a new ALS model which links the current knowledge of genetic factors, ageing and environmental insults. This model provides a mechanism as to how ALS is initiated, with environmental insults playing a critical role. Conclusion The available evidence has suggested that inherited defect(s) could cause mitochondrial dysfunction, which would establish the primary susceptibility to ALS. Further study of the underlying mechanism may shed light on ALS pathogenesis. Environmental insults are a critical trigger for ALS, particularly in the aged individuals with other toxicant susceptible genes. The identification of ALS triggers could lead to preventive strategies for those individuals at risk.http://link.springer.com/article/10.1186/s40035-017-0087-3Amyotrophic lateral sclerosisEnvironmental risk factorsMendelian randomisationMitochondrial dysfunctionTriggerInitiation |
| spellingShingle | Bing Yu Roger Pamphlett Environmental insults: critical triggers for amyotrophic lateral sclerosis Translational Neurodegeneration Amyotrophic lateral sclerosis Environmental risk factors Mendelian randomisation Mitochondrial dysfunction Trigger Initiation |
| title | Environmental insults: critical triggers for amyotrophic lateral sclerosis |
| title_full | Environmental insults: critical triggers for amyotrophic lateral sclerosis |
| title_fullStr | Environmental insults: critical triggers for amyotrophic lateral sclerosis |
| title_full_unstemmed | Environmental insults: critical triggers for amyotrophic lateral sclerosis |
| title_short | Environmental insults: critical triggers for amyotrophic lateral sclerosis |
| title_sort | environmental insults critical triggers for amyotrophic lateral sclerosis |
| topic | Amyotrophic lateral sclerosis Environmental risk factors Mendelian randomisation Mitochondrial dysfunction Trigger Initiation |
| url | http://link.springer.com/article/10.1186/s40035-017-0087-3 |
| work_keys_str_mv | AT bingyu environmentalinsultscriticaltriggersforamyotrophiclateralsclerosis AT rogerpamphlett environmentalinsultscriticaltriggersforamyotrophiclateralsclerosis |