| RRC ID |
74796
|
| 著者 |
Wang Z, Wang X, Shi L, Cai Y, Hu B.
|
| タイトル |
Wolfram syndrome 1b mutation suppresses Mauthner-cell axon regeneration via ER stress signal pathway.
|
| ジャーナル |
Acta Neuropathol Commun
|
| Abstract |
Wolfram Syndrome (WS) is a fatal human inherited disease with symptoms of diabetes, vision decreasing, and neurodegeneration caused by mutations in the endoplasmic reticulum (ER)-resident protein WFS1. WFS1 has been reported to play an important role in glucose metabolism. However, the role of WFS1 in axonal regeneration in the central nervous system has so far remained elusive. Herein, we established a model of the wfs1b globally deficient zebrafish line. wfs1b deficiency severely impeded the Mauthner-cell (M-cell) axon regeneration, which was partly dependent on the ER stress response. The administration of ER stress inhibitor 4-Phenylbutyric acid (4-PBA) promoted M-cell axon regeneration in wfs1b-/- zebrafish larvae, while the ER stress activator Tunicamycin (TM) inhibited M-cell axon regeneration in wfs1b+/+ zebrafish larvae. Moreover, complementation of wfs1b at the single-cell level stimulated M-cell axon regeneration in the wfs1b-/- zebrafish larvae. Altogether, our results revealed that wfs1b promotes M-cell axon regeneration through the ER stress signal pathway and provide new evidence for a therapeutic target for WS and axon degeneration.
|
| 巻・号 |
10(1)
|
| ページ |
184
|
| 公開日 |
2022-12-17
|
| DOI |
10.1186/s40478-022-01484-8
|
| PII |
10.1186/s40478-022-01484-8
|
| PMID |
36527091
|
| PMC |
PMC9758940
|
| MeSH |
Animals
Axons / metabolism
Endoplasmic Reticulum Stress
Humans
Membrane Proteins / genetics
Membrane Proteins / metabolism
Mutation / genetics
Nerve Regeneration
Signal Transduction
Wolfram Syndrome* / genetics
Wolfram Syndrome* / metabolism
Zebrafish / metabolism
|
| IF |
5.883
|
| リソース情報 |
| ゼブラフィッシュ |
Tol-056 |
