PUBLICATION
Loss of GBA in zebrafish leads to dopaminergic neurodegeneration, but overexpression of α-synuclein does not further worsen degeneration
- Authors
- Kodera, K., Matsui, N., Saitoh, A., Matsui, H.
- ID
- ZDB-PUB-220521-8
- Date
- 2022
- Source
- Neuroreport 33: 320-325 (Journal)
- Registered Authors
- Matsui, Hideaki
- Keywords
- none
- MeSH Terms
-
- Animals
- Disease Models, Animal
- Dopamine
- Mutation/genetics
- Neurodegenerative Diseases*/metabolism
- Parkinson Disease*/metabolism
- Zebrafish/metabolism
- alpha-Synuclein/metabolism
- PubMed
- 35594444 Full text @ Neuroreport
Citation
Kodera, K., Matsui, N., Saitoh, A., Matsui, H. (2022) Loss of GBA in zebrafish leads to dopaminergic neurodegeneration, but overexpression of α-synuclein does not further worsen degeneration. Neuroreport. 33:320-325.
Abstract
Objectives Parkinson's disease is a neurodegenerative disorder that causes motor and nonmotor symptoms due to the loss of dopaminergic nerves and is characterized by the presence of Lewy bodies, which are mainly composed of α-synuclein. Glucosylceramidase beta (GBA), which is a causative gene of autosomal recessive Gaucher disease, is also known to be a risk gene for Parkinson's disease. In this study, we tried to detect synergistic effects of α-synuclein accumulation and gba depletion on dopaminergic neurodegeneration in zebrafish.
Methods We generated a transgenic line of zebrafish overexpressing the A53T α-synuclein and gba mutant fish, and analyzed pathologies of α-synuclein aggregation and neurodegeneration.
Results Zebrafish overexpressing the A53T α-synuclein did not exhibit α-synuclein aggregate formation. After the loss of gba function in this mutant α-synuclein transgenic line, we observed the marked presence of α-synuclein aggregates. Loss of gba function in zebrafish resulted in dopaminergic and noradrenergic neurodegeneration but this level of neurodegeneration was not exacerbated by overexpression of mutant α-synuclein.
Conclusions These results indicate that loss of gba function was sufficient to generate a neurodegenerative phenotype in zebrafish regardless of the expression of α-synuclein.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping