PUBLICATION
A New Zebrafish Model to Measure Neuronal α-Synuclein Clearance In Vivo
- Authors
- Lopez, A., Gorb, A., Palha, N., Fleming, A., Rubinsztein, D.C.
- ID
- ZDB-PUB-220530-11
- Date
- 2022
- Source
- Genes 13(5): (Journal)
- Registered Authors
- Fleming, Angeleen
- Keywords
- Parkinson’s disease, aggregation, autophagy, axonal transport, neurodegeneration, protein clearance, zebrafish disease model, α-synuclein
- MeSH Terms
-
- Animals
- Kinetics
- Neurons/metabolism
- Synucleinopathies*
- Zebrafish/genetics
- Zebrafish/metabolism
- alpha-Synuclein*/genetics
- alpha-Synuclein*/metabolism
- PubMed
- 35627253 Full text @ Genes (Basel)
Citation
Lopez, A., Gorb, A., Palha, N., Fleming, A., Rubinsztein, D.C. (2022) A New Zebrafish Model to Measure Neuronal α-Synuclein Clearance In Vivo. Genes. 13(5).
Abstract
The accumulation and aggregation of α-synuclein (α-SYN) is a common characteristic of synucleinopathies, such as Parkinson's Disease (PD), Dementia with Lewy Bodies (DLB) or Multiple System Atrophy (MSA). Multiplications of the wildtype gene of α-SYN (SNCA) and most point mutations make α-SYN more aggregate-prone, and are associated with mitochondrial defects, trafficking obstruction, and impaired proteostasis, which contribute to elevated neuronal death. Here, we present new zebrafish models expressing either human wildtype (wt), or A53T mutant, α-SYN that recapitulate the above-mentioned hallmarks of synucleinopathies. The appropriate clearance of toxic α-SYN has been previously shown to play a key role in maintaining cell homeostasis and survival. However, the paucity of models to investigate α-SYN degradation in vivo limits our understanding of this process. Based on our recently described imaging method for measuring tau protein clearance in neurons in living zebrafish, we fused human SNCA to the photoconvertible protein Dendra2 which enabled analyses of wt and A53T α-SYN clearance kinetics in vivo. Moreover, these zebrafish models can be used to investigate the kinetics of α-SYN aggregation and to study the mechanisms, and potential new targets, controlling the clearance of both soluble and aggregated α-SYN.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping