Dynamics of Onset and Progression in Amyotrophic Lateral Sclerosis
This review focuses on the complexities of amyotrophic lateral sclerosis (ALS) onset, highlighting the insidious nature of the disease and the challenges in defining its precise origin and early pathogenic mechanisms. The clinical presentation of ALS is characterised by progressive muscle weakness a...
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MDPI AG
2025-06-01
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| Series: | Brain Sciences |
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| Online Access: | https://www.mdpi.com/2076-3425/15/6/601 |
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| author | Michael Swash Mamede de Carvalho |
| author_facet | Michael Swash Mamede de Carvalho |
| author_sort | Michael Swash |
| collection | DOAJ |
| description | This review focuses on the complexities of amyotrophic lateral sclerosis (ALS) onset, highlighting the insidious nature of the disease and the challenges in defining its precise origin and early pathogenic mechanisms. The clinical presentation of ALS is characterised by progressive muscle weakness and wasting, often with widespread fasciculations, reflecting lower motor neuron hyperexcitability. The disease’s pathogenesis involves a prolonged preclinical phase of neuronal proteinopathy, particularly TDP-43 accumulation, which eventually leads to motor neuron death and overt ALS. This review discusses the difficulties in detecting this transition and the implications for early therapeutic intervention. It also addresses the involvement of both the upper and lower motor neuron systems, as well as the importance of following presymptomatic patients with genetic mutations. The significance of understanding the distinct processes of TDP-43 deposition and subsequent neuronal degeneration in developing effective treatments is emphasised. |
| format | Article |
| id | doaj-art-e9bef459448747fe8a93936d34dc4faf |
| institution | Kabale University |
| issn | 2076-3425 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Brain Sciences |
| spelling | doaj-art-e9bef459448747fe8a93936d34dc4faf2025-08-20T03:27:28ZengMDPI AGBrain Sciences2076-34252025-06-0115660110.3390/brainsci15060601Dynamics of Onset and Progression in Amyotrophic Lateral SclerosisMichael Swash0Mamede de Carvalho1Barts and the London School of Medicine, Queen Mary University of London, London E1 4NS, UKDepartment of Neurosciences and Mental Health, Centro Hospitalar Universitário Lisboa Norte, 1649-035 Lisboa, PortugalThis review focuses on the complexities of amyotrophic lateral sclerosis (ALS) onset, highlighting the insidious nature of the disease and the challenges in defining its precise origin and early pathogenic mechanisms. The clinical presentation of ALS is characterised by progressive muscle weakness and wasting, often with widespread fasciculations, reflecting lower motor neuron hyperexcitability. The disease’s pathogenesis involves a prolonged preclinical phase of neuronal proteinopathy, particularly TDP-43 accumulation, which eventually leads to motor neuron death and overt ALS. This review discusses the difficulties in detecting this transition and the implications for early therapeutic intervention. It also addresses the involvement of both the upper and lower motor neuron systems, as well as the importance of following presymptomatic patients with genetic mutations. The significance of understanding the distinct processes of TDP-43 deposition and subsequent neuronal degeneration in developing effective treatments is emphasised.https://www.mdpi.com/2076-3425/15/6/601amyotrophic lateral sclerosislower motor neurononsetprogressionupper motor neurontreatment |
| spellingShingle | Michael Swash Mamede de Carvalho Dynamics of Onset and Progression in Amyotrophic Lateral Sclerosis Brain Sciences amyotrophic lateral sclerosis lower motor neuron onset progression upper motor neuron treatment |
| title | Dynamics of Onset and Progression in Amyotrophic Lateral Sclerosis |
| title_full | Dynamics of Onset and Progression in Amyotrophic Lateral Sclerosis |
| title_fullStr | Dynamics of Onset and Progression in Amyotrophic Lateral Sclerosis |
| title_full_unstemmed | Dynamics of Onset and Progression in Amyotrophic Lateral Sclerosis |
| title_short | Dynamics of Onset and Progression in Amyotrophic Lateral Sclerosis |
| title_sort | dynamics of onset and progression in amyotrophic lateral sclerosis |
| topic | amyotrophic lateral sclerosis lower motor neuron onset progression upper motor neuron treatment |
| url | https://www.mdpi.com/2076-3425/15/6/601 |
| work_keys_str_mv | AT michaelswash dynamicsofonsetandprogressioninamyotrophiclateralsclerosis AT mamededecarvalho dynamicsofonsetandprogressioninamyotrophiclateralsclerosis |