期刊
FASEB JOURNAL
卷 33, 期 1, 页码 928-941出版社
FEDERATION AMER SOC EXP BIOL
DOI: 10.1096/fj.201800291R
关键词
aldehyde; ALDH3A2; myelin; sphingolipid; fatty acid 2-hydroxylase
资金
- Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan under the Support Program for Implementation of a New Equipment Sharing System
- Platform Project for Supporting Drug Discovery and Life Science Research (Platform for Drug Discovery, Informatics, and Structural Life Science) from MEXT
- Japan Agency for Medical Research and Development (AMED)
- Ono Medical Research Foundation
- Advanced Research and Development Programs for Medical Innovation (AMED-CREST) [JP18gm0910002]
- MEXT
- Japan Society for the Promotion of Science [JP18H03976, JP18H04664, JP16K08220]
Insulation by myelin lipids is essential to fast action potential conductivity: changes in their quality or amount can cause several neurologic disorders. Sjogren-Larsson syndrome (SLS) is one such disorder, which is caused by mutations in the fatty aldehyde dehydrogenase ALDH3A2. To date, the molecular mechanism underlying SLS pathology has remained unknown. In this study, we found that Aldh3a2 is expressed in oligodendrocytes and neurons in the mouse brain, and neurons of Aldh3a2 knockout (KO) mice exhibited impaired metabolism of the long-chain base, a component of sphingolipids. Aldh3a2 KO mice showed several abnormalities corresponding to SLS symptoms in behavioral tests, including increased paw slips on a balance beam and light-induced anxiety. In their brain tissue, 2-hydroxygalactosylceramide, an important lipid for myelin function and maintenance, was reduced by the inactivation of fatty acid 2-hydroxylase. Our findings provide important new insights into the molecular mechanisms responsible for neural pathogenesis caused by lipid metabolism abnormalities.Kanetake, T., Sassa, T., Nojiri, K., Sawai, M., Hattori, S., Miyakawa, T., Kitamura, T., Kihara, A. Neural symptoms in a gene knockout mouse model of Sjogren-Larsson syndrome are associated with a decrease in 2-hydroxygalactosylceramide.
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