論文 - 詳細
| RRC ID | 79081 |
|---|---|
| 著者 | Miyazaki S, Shimizu N, Miyahara H, Teranishi H, Umeda R, Yano S, Shimada T, Shiraishi H, Komiya K, Katoh A, Yoshimura A, Hanada R, Hanada T. |
| タイトル | DHCR7 links cholesterol synthesis with neuronal development and axonal integrity. |
| ジャーナル | Biochem Biophys Res Commun |
| Abstract |
The DHCR7 enzyme converts 7-DHC into cholesterol. Mutations in DHCR7 can block cholesterol production, leading to abnormal accumulation of 7-DHC and causing Smith-Lemli-Opitz syndrome (SLOS). SLOS is an autosomal recessive disorder characterized by multiple malformations, including microcephaly, intellectual disability, behavior reminiscent of autism, sleep disturbances, and attention-deficit/hyperactivity disorder (ADHD)-like hyperactivity. Although 7-DHC affects neuronal differentiation in ex vivo experiments, the precise mechanism of SLOS remains unclear. We generated Dhcr7 deficient (dhcr7-/-) zebrafish that exhibited key features of SLOS, including microcephaly, decreased neural stem cell pools, and behavioral phenotypes similar to those of ADHD-like hyperactivity. These zebrafish demonstrated compromised myelination, synaptic anomalies, and neurotransmitter imbalances. The axons of the dhcr7-/- zebrafish showed increased lysosomes and attenuated autophagy, suggesting that autophagy-related neuronal homeostasis is disrupted. |
| 巻・号 | 712-713 |
| ページ | 149932 |
| 公開日 | 2024-4-12 |
| DOI | 10.1016/j.bbrc.2024.149932 |
| PII | S0006-291X(24)00468-6 |
| PMID | 38626530 |
| MeSH | Animals Autophagy Axons* / metabolism Cholesterol* / metabolism Lysosomes / metabolism Neurogenesis Neurons / metabolism Oxidoreductases Acting on CH-CH Group Donors* / deficiency Oxidoreductases Acting on CH-CH Group Donors* / genetics Oxidoreductases Acting on CH-CH Group Donors* / metabolism Smith-Lemli-Opitz Syndrome / genetics Smith-Lemli-Opitz Syndrome / metabolism Smith-Lemli-Opitz Syndrome / pathology Zebrafish* / genetics Zebrafish* / metabolism Zebrafish Proteins / genetics Zebrafish Proteins / metabolism |
| IF | 2.985 |
| 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 | 2 |
| 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 | Tg(Huc:Kaede)rw0130a Tg(gfap:dTomato) Tg(6xTcf/LefBS-miniP:d2EGFP)isi04 |