TDP-43 dysregulation and neuromuscular junction disruption in amyotrophic lateral sclerosis
Abstract Amyotrophic lateral sclerosis (ALS) is a disease characterized by upper and lower motor neuron (MN) loss with a signature feature of cytoplasmic aggregates containing TDP-43, which are detected in nearly all patients. Mutations in the gene that encodes TDP-43 (TARBDP) are known to result in...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
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BMC
2022-12-01
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| Series: | Translational Neurodegeneration |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s40035-022-00331-z |
| _version_ | 1797973503238995968 |
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| author | Sarah Lépine Maria José Castellanos-Montiel Thomas Martin Durcan |
| author_facet | Sarah Lépine Maria José Castellanos-Montiel Thomas Martin Durcan |
| author_sort | Sarah Lépine |
| collection | DOAJ |
| description | Abstract Amyotrophic lateral sclerosis (ALS) is a disease characterized by upper and lower motor neuron (MN) loss with a signature feature of cytoplasmic aggregates containing TDP-43, which are detected in nearly all patients. Mutations in the gene that encodes TDP-43 (TARBDP) are known to result in both familial and sporadic ALS. In ALS, disruption of neuromuscular junctions (NMJs) constitutes a critical event in disease pathogenesis, leading to denervation atrophy, motor impairments and disability. Morphological defects and impaired synaptic transmission at NMJs have been reported in several TDP-43 animal models and in vitro, linking TDP-43 dysregulation to the loss of NMJ integrity in ALS. Through the lens of the dying-back and dying-forward hypotheses of ALS, this review discusses the roles of TDP-43 related to synaptic function, with a focus on the potential molecular mechanisms occurring within MNs, skeletal muscles and glial cells that may contribute to NMJ disruption in ALS. |
| first_indexed | 2024-04-11T04:04:53Z |
| format | Article |
| id | doaj.art-296d3560e94946f1abcb4b4054464963 |
| institution | Directory Open Access Journal |
| issn | 2047-9158 |
| language | English |
| last_indexed | 2024-04-11T04:04:53Z |
| publishDate | 2022-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Translational Neurodegeneration |
| spelling | doaj.art-296d3560e94946f1abcb4b40544649632023-01-01T12:25:59ZengBMCTranslational Neurodegeneration2047-91582022-12-0111112410.1186/s40035-022-00331-zTDP-43 dysregulation and neuromuscular junction disruption in amyotrophic lateral sclerosisSarah Lépine0Maria José Castellanos-Montiel1Thomas Martin Durcan2The Neuro’s Early Drug Discovery Unit (EDDU), Department of Neurology and Neurosurgery, Montreal Neurological Institute-Hospital, McGill UniversityThe Neuro’s Early Drug Discovery Unit (EDDU), Department of Neurology and Neurosurgery, Montreal Neurological Institute-Hospital, McGill UniversityThe Neuro’s Early Drug Discovery Unit (EDDU), Department of Neurology and Neurosurgery, Montreal Neurological Institute-Hospital, McGill UniversityAbstract Amyotrophic lateral sclerosis (ALS) is a disease characterized by upper and lower motor neuron (MN) loss with a signature feature of cytoplasmic aggregates containing TDP-43, which are detected in nearly all patients. Mutations in the gene that encodes TDP-43 (TARBDP) are known to result in both familial and sporadic ALS. In ALS, disruption of neuromuscular junctions (NMJs) constitutes a critical event in disease pathogenesis, leading to denervation atrophy, motor impairments and disability. Morphological defects and impaired synaptic transmission at NMJs have been reported in several TDP-43 animal models and in vitro, linking TDP-43 dysregulation to the loss of NMJ integrity in ALS. Through the lens of the dying-back and dying-forward hypotheses of ALS, this review discusses the roles of TDP-43 related to synaptic function, with a focus on the potential molecular mechanisms occurring within MNs, skeletal muscles and glial cells that may contribute to NMJ disruption in ALS.https://doi.org/10.1186/s40035-022-00331-zAmyotrophic lateral sclerosisDenervationNeuromuscular junctionTDP-43Dying-backDying-forward |
| spellingShingle | Sarah Lépine Maria José Castellanos-Montiel Thomas Martin Durcan TDP-43 dysregulation and neuromuscular junction disruption in amyotrophic lateral sclerosis Translational Neurodegeneration Amyotrophic lateral sclerosis Denervation Neuromuscular junction TDP-43 Dying-back Dying-forward |
| title | TDP-43 dysregulation and neuromuscular junction disruption in amyotrophic lateral sclerosis |
| title_full | TDP-43 dysregulation and neuromuscular junction disruption in amyotrophic lateral sclerosis |
| title_fullStr | TDP-43 dysregulation and neuromuscular junction disruption in amyotrophic lateral sclerosis |
| title_full_unstemmed | TDP-43 dysregulation and neuromuscular junction disruption in amyotrophic lateral sclerosis |
| title_short | TDP-43 dysregulation and neuromuscular junction disruption in amyotrophic lateral sclerosis |
| title_sort | tdp 43 dysregulation and neuromuscular junction disruption in amyotrophic lateral sclerosis |
| topic | Amyotrophic lateral sclerosis Denervation Neuromuscular junction TDP-43 Dying-back Dying-forward |
| url | https://doi.org/10.1186/s40035-022-00331-z |
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