論文 - 詳細
| RRC ID | 83105 |
|---|---|
| 著者 | Otte CG, Fortuna TR, Mann JR, Gleixner AM, Ramesh N, Pyles NJ, Pandey UB, Donnelly CJ. |
| タイトル | Optogenetic TDP-43 nucleation induces persistent insoluble species and progressive motor dysfunction in vivo. |
| ジャーナル | Neurobiol Dis |
| Abstract |
TDP-43 is a predominantly nuclear DNA/RNA binding protein that is often mislocalized into insoluble cytoplasmic inclusions in post-mortem patient tissue in a variety of neurodegenerative disorders including Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal dementia (FTD). The underlying causes of TDP-43 proteinopathies remain unclear, but recent studies indicate the formation of these protein assemblies is driven by aberrant phase transitions of RNA deficient TDP-43. Technical limitations have prevented our ability to understand how TDP-43 proteinopathy relates to disease pathogenesis. Current animal models of TDP-43 proteinopathy often rely on overexpression of wild-type TDP-43 to non-physiological levels that may initiate neurotoxicity through nuclear gain of function mechanisms, or by the expression of disease-causing mutations found in only a fraction of ALS patients. New technologies allowing for light-responsive control of subcellular protein crowding provide a promising approach to drive intracellular protein aggregation, as we have previously demonstrated in vitro. Here we present a model for the optogenetic induction of TDP-43 proteinopathy in Drosophila that recapitulates key features of patient pathology, including detergent insoluble cytoplamsic inclusions and progressive motor dysfunction. |
| 巻・号 | 146 |
| ページ | 105078 |
| 公開日 | 2020-12-1 |
| DOI | 10.1016/j.nbd.2020.105078 |
| PII | S0969-9961(20)30353-3 |
| PMID | 32927062 |
| PMC | PMC9040199 |
| MeSH | Animals Cell Nucleus / metabolism DNA-Binding Proteins / metabolism Drosophila Frontotemporal Dementia / genetics* Frontotemporal Dementia / pathology Inclusion Bodies / metabolism* Mutation / genetics* Neurodegenerative Diseases / genetics Neurodegenerative Diseases / metabolism Neurons / metabolism Optogenetics / methods TDP-43 Proteinopathies / genetics* |
| IF | 5.332 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 13 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ゼブラフィッシュ | SAIGFF213A, mnr2b-hs:EGFP-TDP-43z, UAS:opTDP-43z |