PUBLICATION
DHCR7 links cholesterol synthesis with neuronal development and axonal integrity
- Authors
- 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.
- ID
- ZDB-PUB-240417-4
- Date
- 2024
- Source
- Biochemical and Biophysical Research Communications 712-713: 149932149932 (Journal)
- Registered Authors
- Hanada, Reiko, Hanada, Toshikatsu
- Keywords
- Brain, Cholesterol, DHCR7, SLOS, Zebrafish
- MeSH Terms
-
- 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
- PubMed
- 38626530 Full text @ Biochem. Biophys. Res. Commun.
Citation
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. (2024) DHCR7 links cholesterol synthesis with neuronal development and axonal integrity. Biochemical and Biophysical Research Communications. 712-713:149932149932.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping