PUBLICATION
TDP-43 Regulation of AChE Expression Can Mediate ALS-Like Phenotype in Zebrafish
- Authors
- Campanari, M.L., Marian, A., Ciura, S., Kabashi, E.
- ID
- ZDB-PUB-210128-18
- Date
- 2021
- Source
- Cells 10(2): (Journal)
- Registered Authors
- Keywords
- TAR DNA-binding protein 43 (TDP-43), acetylcholinesterase (AChE), amyotrophic lateral sclerosis (ALS), knockdown (KD), neuromuscular junction (NMJ)
- MeSH Terms
-
- Acetylcholinesterase/metabolism*
- Amyotrophic Lateral Sclerosis/metabolism*
- Amyotrophic Lateral Sclerosis/pathology*
- Animals
- DNA-Binding Proteins/metabolism*
- Epistasis, Genetic
- Gene Knockdown Techniques
- Neuromuscular Junction/pathology
- Phenotype
- Protein Binding
- Zebrafish/metabolism*
- Zebrafish Proteins/metabolism*
- PubMed
- 33499374 Full text @ Cells
Citation
Campanari, M.L., Marian, A., Ciura, S., Kabashi, E. (2021) TDP-43 Regulation of AChE Expression Can Mediate ALS-Like Phenotype in Zebrafish. Cells. 10(2):.
Abstract
The "distal axonopathy" hypothesis in amyotrophic lateral sclerosis (ALS) proposes that pathological changes occur at the neuromuscular junction (NMJ) early in the disease. While acetylcholinesterase (AChE) plays an important role in the functionality of the NMJ, its potential role in ALS remains unexplored. Here, we identified AChE as a limiting factor regulating muscle/motor neuron connection in a vertebrate model of ALS. Knockdown of the TAR DNA-binding protein 43 (TDP-43) orthologue in zebrafish resulted in early defects of motor functions coupled with NMJ disassembly. We found that a partially depleted tdp-43 caused a decrease of ache expression. Importantly, human AChE overexpression reduced the phenotypic defects in the tdp-43 loss of function model, with amelioration of post- and pre-synaptic deficits at the NMJ. In conclusion, our results provide a better understanding of the role of TDP-43 in the NMJ organization and indicate AChE as a contributing factor in the pathology of ALS. In particular, it may be implicated in the early defects that characterize NMJs in this major neurodegenerative disorder.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping