History of ALS and the competing theories on pathogenesis: IFCN handbook chapter
Amyotrophic lateral sclerosis (ALS) is a rapidly progressive neurodegenerative disorder of the human motor system, first described in the 19th Century. The etiology of ALS appears to be multifactorial, with a complex interaction of genetic, epigenetic, and environmental factors underlying the onset...
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2024-01-01
|
| Series: | Clinical Neurophysiology Practice |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2467981X2300032X |
| _version_ | 1797382853195988992 |
|---|---|
| author | Andrew Eisen Steve Vucic Hiroshi Mitsumoto |
| author_facet | Andrew Eisen Steve Vucic Hiroshi Mitsumoto |
| author_sort | Andrew Eisen |
| collection | DOAJ |
| description | Amyotrophic lateral sclerosis (ALS) is a rapidly progressive neurodegenerative disorder of the human motor system, first described in the 19th Century. The etiology of ALS appears to be multifactorial, with a complex interaction of genetic, epigenetic, and environmental factors underlying the onset of disease. Importantly, there are no known naturally occurring animal models, and transgenic mouse models fail to faithfully reproduce ALS as it manifests in patients. Debate as to the site of onset of ALS remain, with three competing theories proposed, including (i) the dying-forward hypothesis, whereby motor neuron degeneration is mediated by hyperexcitable corticomotoneurons via an anterograde transsynaptic excitotoxic mechanism, (ii) dying-back hypothesis, proposing the ALS begins in the peripheral nervous system with a toxic factor(s) retrogradely transported into the central nervous system and mediating upper motor neuron dysfunction, and (iii) independent hypothesis, suggesting that upper and lower motor neuron degenerated independently. Transcranial magnetic stimulation studies, along with pathological and genetic findings have supported the dying forward hypothesis theory, although the science is yet to be settled. The review provides a historical overview of ALS, discusses phenotypes and likely pathogenic mechanisms. |
| first_indexed | 2024-03-08T21:12:22Z |
| format | Article |
| id | doaj.art-6a9761c4835c44d7b149f438d8a588ca |
| institution | Directory Open Access Journal |
| issn | 2467-981X |
| language | English |
| last_indexed | 2024-03-08T21:12:22Z |
| publishDate | 2024-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Clinical Neurophysiology Practice |
| spelling | doaj.art-6a9761c4835c44d7b149f438d8a588ca2023-12-22T05:33:52ZengElsevierClinical Neurophysiology Practice2467-981X2024-01-019112History of ALS and the competing theories on pathogenesis: IFCN handbook chapterAndrew Eisen0Steve Vucic1Hiroshi Mitsumoto2Division of Neurology, Department of Medicine, University of British Columbia, Canada; Corresponding author at: Division of Neurology, Department of Medicine, University of British Columbia, Canada.Director Brain and Nerve Research Center, Clinical School, University of Sydney, AustraliaWesley J. Howe Professor of Neurology, Columbia University, The Neurological Institute of New York, and New York-Presbyterian Hospital/Columbia University Medical Center, United StatesAmyotrophic lateral sclerosis (ALS) is a rapidly progressive neurodegenerative disorder of the human motor system, first described in the 19th Century. The etiology of ALS appears to be multifactorial, with a complex interaction of genetic, epigenetic, and environmental factors underlying the onset of disease. Importantly, there are no known naturally occurring animal models, and transgenic mouse models fail to faithfully reproduce ALS as it manifests in patients. Debate as to the site of onset of ALS remain, with three competing theories proposed, including (i) the dying-forward hypothesis, whereby motor neuron degeneration is mediated by hyperexcitable corticomotoneurons via an anterograde transsynaptic excitotoxic mechanism, (ii) dying-back hypothesis, proposing the ALS begins in the peripheral nervous system with a toxic factor(s) retrogradely transported into the central nervous system and mediating upper motor neuron dysfunction, and (iii) independent hypothesis, suggesting that upper and lower motor neuron degenerated independently. Transcranial magnetic stimulation studies, along with pathological and genetic findings have supported the dying forward hypothesis theory, although the science is yet to be settled. The review provides a historical overview of ALS, discusses phenotypes and likely pathogenic mechanisms.http://www.sciencedirect.com/science/article/pii/S2467981X2300032XAmyotrophic lateral sclerosisCharcotDying-forwardMotor neuron disease |
| spellingShingle | Andrew Eisen Steve Vucic Hiroshi Mitsumoto History of ALS and the competing theories on pathogenesis: IFCN handbook chapter Clinical Neurophysiology Practice Amyotrophic lateral sclerosis Charcot Dying-forward Motor neuron disease |
| title | History of ALS and the competing theories on pathogenesis: IFCN handbook chapter |
| title_full | History of ALS and the competing theories on pathogenesis: IFCN handbook chapter |
| title_fullStr | History of ALS and the competing theories on pathogenesis: IFCN handbook chapter |
| title_full_unstemmed | History of ALS and the competing theories on pathogenesis: IFCN handbook chapter |
| title_short | History of ALS and the competing theories on pathogenesis: IFCN handbook chapter |
| title_sort | history of als and the competing theories on pathogenesis ifcn handbook chapter |
| topic | Amyotrophic lateral sclerosis Charcot Dying-forward Motor neuron disease |
| url | http://www.sciencedirect.com/science/article/pii/S2467981X2300032X |
| work_keys_str_mv | AT andreweisen historyofalsandthecompetingtheoriesonpathogenesisifcnhandbookchapter AT stevevucic historyofalsandthecompetingtheoriesonpathogenesisifcnhandbookchapter AT hiroshimitsumoto historyofalsandthecompetingtheoriesonpathogenesisifcnhandbookchapter |