HUST Found New Molecular Mechanism for Retinitis Pigmentosa

September 25, 2018

On September 12th, the famous biomedical journal Autophagy online published a reach article entitled “CERKL regulates autophagy via the NAD-dependent deacetylase SIRT1”. This work is done by Dr. Liu Mugen and his colleagues. Professor Liu is a professor of the College of life science and technology of Huazhong University of Science and Technology. Hu Xuebin, a PhD candidate, and Dr. Lu zhaojing, are co-first authors for this paper. Prof. Liu Mugen and Prof. Tang zhaohui are co-corresponding authors.

Retinitis pigmentosa (RP) is a group of inherited retinal degenerative diseases characterized by progressive loss of photoreceptor function. Currently, there is no good treatment for patients with these diseases. Liu’s group are focusing on the discovery the molecular pathological mechanism of RP. The group have collected patients with autosomal recessive RP families and found CERKL is an important disease-causing gene for RPArch Ophthalmol. 2009;127(8):1077-8. They also studies found that CERKL protected retina photoreceptors against ROSBiochim Biophys Acta. 2014;1842(7):1121-9; Cell Signal. 2015;27(11):2314-23. In order to explore the pathogenic mechanism of RP pathogenic gene, the research team successfully constructed the world's first animal model of CERKL gene mutation leading to RP, and found that in the CERKL knockout zebrafish, the phagocytosis of the photoreceptor outer segment by the retinal pigment epithelial cells (RPE) was impaired, leading to retinal degenerative diseaseHum Mol Genet. 2017; 15;26(12):2335-2345.

In the autophagy article, Liu’s group reported that suppressing CERKL results in impaired autophagy in RPE and photoreceptors. Further study showed that CERKL regulated autophagy by stabilizing SIRT1. CERKL directly interacts with SIRT1 and may regulate its phosphorylation to stabilize SIRT1. The findings have suggested a novel molecular mechanism for the maintenance of the homeostasis and visual function in the retina.

The studies was supported by grants including the National Natural Science Foundation of China. These findings not only reveal the new pathogenesis of RP, but also may be important for development of new clinical treatment strategies and the selection of therapeutic drugs for such diseases.

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