Disease propagation in amyotrophic lateral sclerosis (ALS): an interplay between genetics and environment
Abstract Amyotrophic lateral sclerosis (ALS) is a progressive, fatal disease affecting the neuromuscular system. While there have been a number of important genetic discoveries, there are no therapeutics capable of stopping its insidious progression. Lessons from clinical histories reveal that ALS c...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
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BMC
2020-06-01
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| Series: | Journal of Neuroinflammation |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12974-020-01849-7 |
| _version_ | 1818514880098992128 |
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| author | Sarah Schram Jeffrey A. Loeb Fei Song |
| author_facet | Sarah Schram Jeffrey A. Loeb Fei Song |
| author_sort | Sarah Schram |
| collection | DOAJ |
| description | Abstract Amyotrophic lateral sclerosis (ALS) is a progressive, fatal disease affecting the neuromuscular system. While there have been a number of important genetic discoveries, there are no therapeutics capable of stopping its insidious progression. Lessons from clinical histories reveal that ALS can start focally at a single limb, but then segmentally spread up and down the spinal cord as well as in the motor cortex and cortex of frontal and temporal lobes until respiratory muscles fail. With or without a clear genetic etiology, often there is no explanation as to why it starts in one region of the body versus another. Similarly, once the disease starts the mechanisms by which the neurodegenerative process spreads are not known. Here, we summarize recent work in animal models that support the hypothesis that critical environmental contributions, such as a nerve injury, can initiate the disease process. We also propose that pathological axoglial signaling by the glial growth factor neuregulin-1 leads to the slow propagation of neuroinflammation resulting in neurodegeneration up and down the spinal cord and that locally applied drugs that block neuregulin-1 signaling could slow or halt the spread of disease. |
| first_indexed | 2024-12-11T00:21:44Z |
| format | Article |
| id | doaj.art-a5314c61cbb14bceb91b56bf47501dd2 |
| institution | Directory Open Access Journal |
| issn | 1742-2094 |
| language | English |
| last_indexed | 2024-12-11T00:21:44Z |
| publishDate | 2020-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Neuroinflammation |
| spelling | doaj.art-a5314c61cbb14bceb91b56bf47501dd22022-12-22T01:27:43ZengBMCJournal of Neuroinflammation1742-20942020-06-011711710.1186/s12974-020-01849-7Disease propagation in amyotrophic lateral sclerosis (ALS): an interplay between genetics and environmentSarah Schram0Jeffrey A. Loeb1Fei Song2Department of Neurology and Rehabilitation, University of Illinois at ChicagoDepartment of Neurology and Rehabilitation, University of Illinois at ChicagoDepartment of Neurology and Rehabilitation, University of Illinois at ChicagoAbstract Amyotrophic lateral sclerosis (ALS) is a progressive, fatal disease affecting the neuromuscular system. While there have been a number of important genetic discoveries, there are no therapeutics capable of stopping its insidious progression. Lessons from clinical histories reveal that ALS can start focally at a single limb, but then segmentally spread up and down the spinal cord as well as in the motor cortex and cortex of frontal and temporal lobes until respiratory muscles fail. With or without a clear genetic etiology, often there is no explanation as to why it starts in one region of the body versus another. Similarly, once the disease starts the mechanisms by which the neurodegenerative process spreads are not known. Here, we summarize recent work in animal models that support the hypothesis that critical environmental contributions, such as a nerve injury, can initiate the disease process. We also propose that pathological axoglial signaling by the glial growth factor neuregulin-1 leads to the slow propagation of neuroinflammation resulting in neurodegeneration up and down the spinal cord and that locally applied drugs that block neuregulin-1 signaling could slow or halt the spread of disease.http://link.springer.com/article/10.1186/s12974-020-01849-7Nerve injury-mediated neuroinflammationNeuronal-glial communication through glial growth factor neuregulinInhibition of neuregulin-mediated inflammation |
| spellingShingle | Sarah Schram Jeffrey A. Loeb Fei Song Disease propagation in amyotrophic lateral sclerosis (ALS): an interplay between genetics and environment Journal of Neuroinflammation Nerve injury-mediated neuroinflammation Neuronal-glial communication through glial growth factor neuregulin Inhibition of neuregulin-mediated inflammation |
| title | Disease propagation in amyotrophic lateral sclerosis (ALS): an interplay between genetics and environment |
| title_full | Disease propagation in amyotrophic lateral sclerosis (ALS): an interplay between genetics and environment |
| title_fullStr | Disease propagation in amyotrophic lateral sclerosis (ALS): an interplay between genetics and environment |
| title_full_unstemmed | Disease propagation in amyotrophic lateral sclerosis (ALS): an interplay between genetics and environment |
| title_short | Disease propagation in amyotrophic lateral sclerosis (ALS): an interplay between genetics and environment |
| title_sort | disease propagation in amyotrophic lateral sclerosis als an interplay between genetics and environment |
| topic | Nerve injury-mediated neuroinflammation Neuronal-glial communication through glial growth factor neuregulin Inhibition of neuregulin-mediated inflammation |
| url | http://link.springer.com/article/10.1186/s12974-020-01849-7 |
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