論文 - 詳細
| RRC ID | 57245 |
|---|---|
| 著者 | Hosaka Y, Inoshita T, Shiba-Fukushima K, Cui C, Arano T, Imai Y, Hattori N. |
| タイトル | Reduced TDP-43 Expression Improves Neuronal Activities in a Drosophila Model of Perry Syndrome. |
| ジャーナル | EBioMedicine |
| Abstract |
Parkinsonian Perry syndrome, involving mutations in the dynein motor component dynactin or p150Glued, is characterized by TDP-43 pathology in affected brain regions, including the substantia nigra. However, the molecular relationship between p150Glued and TDP-43 is largely unknown. Here, we report that a reduction in TDP-43 protein levels alleviates the synaptic defects of neurons expressing the Perry mutant p150G50R in Drosophila. Dopaminergic expression of p150G50R, which decreases dopamine release, disrupts motor ability and reduces the lifespan of Drosophila. p150G50R expression also causes aggregation of dense core vesicles (DCVs), which contain monoamines and neuropeptides, and disrupts the axonal flow of DCVs, thus decreasing synaptic strength. The above phenotypes associated with Perry syndrome are improved by the removal of a copy of Drosophila TDP-43 TBPH, thus suggesting that the stagnation of axonal transport by dynactin mutations promotes TDP-43 aggregation and interferes with the dynamics of DCVs and synaptic activities. |
| 巻・号 | 21 |
| ページ | 218-227 |
| 公開日 | 2017-7-1 |
| DOI | 10.1016/j.ebiom.2017.06.002 |
| PII | S2352-3964(17)30230-X |
| PMID | 28625517 |
| PMC | PMC5514405 |
| MeSH | Action Potentials Animals Axonal Transport DNA-Binding Proteins / genetics* DNA-Binding Proteins / metabolism Depression / genetics Depression / metabolism Depression / physiopathology Disease Models, Animal Dopamine / metabolism Drosophila Drosophila Proteins / genetics* Drosophila Proteins / metabolism Gene Expression Regulation* Hypoventilation / genetics* Hypoventilation / metabolism Hypoventilation / physiopathology* Immunohistochemistry Male Motor Activity Motor Neurons / metabolism Motor Neurons / ultrastructure Mutation Neurons / metabolism* Neurons / ultrastructure Parkinsonian Disorders / genetics* Parkinsonian Disorders / metabolism Parkinsonian Disorders / physiopathology* Synaptic Vesicles / metabolism |
| IF | 6.68 |
| 引用数 | 3 |
| リソース情報 | |
| ショウジョウバエ | |