期刊
FREE RADICAL BIOLOGY AND MEDICINE
卷 152, 期 -, 页码 797-809出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.freeradbiomed.2020.01.177
关键词
X-linked adrenoleukodystrophy; Axonal degeneration; Hypodermis; Mitochondria redox imbalance; Lipid droplets; Peroxisomes
资金
- Autonomous Government of Catalonia [2017SGR1206]
- Spanish Ministry of Science and Competitivity [PC0009/003, PI1100968]
- Instituto de Salud Carlos III through the grants [Miguel Servet program] (European Social Fund. ESF investing in your future) [CPII16/00016]
- Center for Biomedical Research on Rare Diseases (CIBERER)
- MRC [MC_UU_00015/3] Funding Source: UKRI
Adrenoleukodystrophy is a neurometabolic disorder caused by a defective peroxisomal ABCD1 transporter of very long-chain fatty acids (VLCFAs). Its pathogenesis is incompletely understood. Here we characterize a nematode model of X-ALD with loss of the pmp-4 gene, the worm orthologue of ABCD1. These mutants recapitulate the hallmarks of X-ALD: i) VLCFAs accumulation and impaired mitochondrial redox homeostasis and ii) axonal damage coupled to locomotor dysfunction. Furthermore, we identify a novel role for PMP-4 in modulating lipid droplet dynamics. Importantly, we show that the mitochondria targeted antioxidant MitoQ normalizes lipid droplets size, and prevents axonal degeneration and locomotor disability, highlighting its therapeutic potential. Moreover, PMP-4 acting solely in the hypodermis rescues axonal and locomotion abnormalities, suggesting a myelin-like role for the hypodermis in providing essential peroxisomal functions for the nematode nervous system.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据