PUBLICATION
[Optogenetic interrogation of TDP-43 cytotoxicity in a zebrafish ALS model]
- Authors
- Asakawa, K., Handa, H., Kawakami, K.
- ID
- ZDB-PUB-230104-13
- Date
- 2023
- Source
- Nihon yakurigaku zasshi. Folia pharmacologica Japonica 158: 162016-20 (Journal)
- Registered Authors
- Asakawa, Kazuhide, Kawakami, Koichi
- Keywords
- none
- MeSH Terms
-
- Amyotrophic Lateral Sclerosis*/genetics
- Amyotrophic Lateral Sclerosis*/metabolism
- Amyotrophic Lateral Sclerosis*/pathology
- Animals
- DNA-Binding Proteins/genetics
- DNA-Binding Proteins/metabolism
- Motor Neurons/metabolism
- Motor Neurons/pathology
- Optogenetics
- Zebrafish/metabolism
- PubMed
- 36596480 Full text @ Nippon Yakurigaku Zasshi
Citation
Asakawa, K., Handa, H., Kawakami, K. (2023) [Optogenetic interrogation of TDP-43 cytotoxicity in a zebrafish ALS model]. Nihon yakurigaku zasshi. Folia pharmacologica Japonica. 158:162016-20.
Abstract
TAR DNA-binding protein 43 (TDP-43) is an evolutionarily conserved RNA/DNA-binding protein that is nuclear-enriched in healthy cells, but deposited in the cytoplasm as aggregates in affected neurons in certain neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). We have previously developed an optogenetic TDP-43 variant (opTDP-43h) whose oligomerization status can be modulated via the CRY2olig tag, which self-assembles upon absorption of blue light. Illumination of zebrafish spinal motor neurons expressing opTDP-43h with a blue light triggers its cytoplasmic mislocalization, eventually leading to cytoplasmic deposition of opTDP-43h aggregates. Intriguingly, a light illumination-dependent transient opTDP-43 mislocalization can halt motor axon outgrowth, even in the absence of cytoplasmic deposition of opTDP-43 aggregates. These observations point toward an oligomerization-dependent, but aggregation-independent, cytotoxic effect of TDP-43 that might contribute to pathogenesis of ALS. In the present review, we would like to overview the zebrafish ALS model based on the optogenetic TDP-43, and then discuss about the potential mechanisms of TDP-43 cytotoxicity that trigger and/or promote motor neuron degeneration in ALS.
Errata / Notes
Paper not written in English.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping