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The DOI matches its Crossref record; 5 of the 5 references it cites were found in a registry or an index.

Lanosterol reverses protein aggregation in cataracts

Zhao, Ling, Chen, Xiang-Jun, Zhu, Jie, Xi, Yi-Bo, Yang, Xu, Hu, Li-Dan, Ouyang, Hong, Patel, Sherrina H., Jin, Xin, Lin, Danni, Wu, Frances, Flagg, Ken, Cai, Huimin, Li, Gen, Cao, Guiqun, Lin, Ying, Chen, Daniel, Wen, Cindy, Chung, Christopher, Wang, Yandong, Qiu, Austin, Yeh, Emily, Wang, Wenqiu, Hu, Xun, Grob, Seanna, Abagyan, Ruben, Su, Zhiguang, Tjondro, Harry Christianto, Zhao, Xi-Juan, Luo, Hongrong, Hou, Rui, Jefferson, J., Perry, P., Gao, Weiwei, Kozak, Igor, Granet, David, Li, Yingrui, Sun, Xiaodong, Wang, Jun, Zhang, Liangfang, Liu, Yizhi, Yan, Yong-Bin, Zhang, Kang·2015·Nature
DOI 10.1038/nature14650
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Abstract

The human lens is comprised largely of crystallin proteins assembled into a highly ordered, interactive macro-structure essential for lens transparency and refractive index. Any disruption of intra- or inter-protein interactions will alter this delicate structure, exposing hydrophobic surfaces, with consequent protein aggregation and cataract formation. Cataracts are the most common cause of blindness worldwide, affecting tens of millions of people, and currently the only treatment is surgical removal of cataractous lenses. The precise mechanisms by which lens proteins both prevent aggregation and maintain lens transparency are largely unknown. Lanosterol is an amphipathic molecule enriched in the lens. It is synthesized by lanosterol synthase (LSS) in a key cyclization reaction of a cholesterol synthesis pathway. Here we identify two distinct homozygous LSS missense mutations (W581R and G588S) in two families with extensive congenital cataracts. Both of these mutations affect highly conserved amino acid residues and impair key catalytic functions of LSS. Engineered expression of wild-type, but not mutant, LSS prevents intracellular protein aggregation of various cataract-causing mutant crystallins. Treatment by lanosterol, but not cholesterol, significantly decreased preformed protein aggregates both in vitro and in cell-transfection experiments. We further show that lanosterol treatment could reduce cataract severity and increase transparency in dissected rabbit cataractous…

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  • In a similar gene therapy approach, the gene encoding for CYP46A1 was delivered into striatal neurons of HD mice by use of an AAVrh10 vector.

    “In a similar gene therapy approach, the gene encoding for CYP46A1, the enzyme that converts cholesterol into the neuronal cholesterol catabolite 24S-OHC, was delivered into striatal neurons of HD mice by use of an AAVrh10 vector 55,56 .”

    From SREBP2 gene therapy targeting striatal astrocytes ameliorates Huntington’s disease phenotypes (2021) · cites this paper as [55]

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Metadata

Authors
Zhao, L., Chen, X.-J., Zhu, J., Xi, Y.-B., Yang, X., Hu, L.-D., Ouyang, H., Patel, S. H., Jin, X., Lin, D., Wu, F., Flagg, K., Cai, H., Li, G., Cao, G., Lin, Y., Chen, D., Wen, C., Chung, C., Wang, Y., Qiu, A., Yeh, E., Wang, W., Hu, X., Grob, S., Abagyan, R., Su, Z., Tjondro, H. C., Zhao, X.-J., Luo, H., Hou, R., Jefferson, J., Perry, P., Gao, W., Kozak, I., Granet, D., Li, Y., Sun, X., Wang, J., Zhang, L., Liu, Y., Yan, Y.-B., & Zhang, K.
Venue
Nature
Publisher
Springer Science and Business Media LLC
Published
2015-07-22
Volume
523
Issue
7562
Pages
607-611
ISSN
  • 0028-0836
  • 1476-4687
DOI
10.1038/nature14650
Cited by
423
References
5
Language
en
Update notices
erratum (2015-08-26)
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