期刊
JOURNAL OF ANATOMY
卷 241, 期 5, 页码 1089-1107出版社
WILEY
DOI: 10.1111/joa.13463
关键词
C9orf72; denervation; dying-back; FUS; NMJ; SOD1; TDP-43
资金
- King Abdulaziz University through the Saudi Cultural Bureau, London
- Anatomical Society
- My Name'5 Doddie Foundation
Amyotrophic lateral sclerosis (ALS) is a motor neuron disease with a heterogeneous clinical and genetic phenotype, and mouse models have shown variable disease progression at the neuromuscular junction (NMJ). Models with SOD1, TARDBP, and FUS mutations exhibit early NMJ dysfunction as a common factor, while C9ORF72 models do not follow the same pattern. Further study into the timing of NMJ pathology in newer ALS mouse models will confirm its pivotal role in ALS pathogenesis.
Amyotrophic lateral sclerosis (ALS) is a motor neuron disease with an extremely heterogeneous clinical and genetic phenotype. In our efforts to find therapies for ALS, the scientific community has developed a plethora of mouse models, each with their own benefits and drawbacks. The peripheral nervous system, specifically the neuromuscular junction (NMJ), is known to be affected in ALS patients and shows marked dysfunction across mouse models. Evidence of pathology at the NMJ includes denervated NMJs, changes in endplate size and loss of terminal Schwann cells. This review compares the temporal disease progression with severity of disease at the NMJ in mouse models with the most commonly mutated genes in ALS patients (SOD1, C9ORF72, TARDBP and FUS). Despite variability, early NMJ dysfunction seems to be a common factor in models with SOD1, TARDBP and FUS mutations, while C9ORF72 models do not appear to follow the same pattern of pathology. Further work into determining the timing of NMJ pathology, particularly in newer ALS mouse models, will confirm its pivotal role in ALS pathogenesis and therefore highlight the NMJ as a potential therapeutic target.
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