Balancing the Photoreceptor Proteome: Proteostasis Network Therapeutics for Inherited Retinal Disease

Genes

Ronald Roepman¹  Siebren Faber¹ 

[1] Department of Human Genetics and Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Geert Grooteplein Zuid 10, 6525 GA Nijmegen, The Netherlands;

关键词: protein trafficking;    protein folding;    protein degradation;    chaperones;    chaperonins;    heat shock response;    unfolded protein response;    autophagy;    therapy;   

DOI  :  10.3390/genes10080557

来源: DOAJ

【 摘 要 】

The light sensing outer segments of photoreceptors (PRs) are renewed every ten days due to their high photoactivity, especially of the cones during daytime vision. This demands a tremendous amount of energy, as well as a high turnover of their main biosynthetic compounds, membranes, and proteins. Therefore, a refined proteostasis network (PN), regulating the protein balance, is crucial for PR viability. In many inherited retinal diseases (IRDs) this balance is disrupted leading to protein accumulation in the inner segment and eventually the death of PRs. Various studies have been focusing on therapeutically targeting the different branches of the PR PN to restore the protein balance and ultimately to treat inherited blindness. This review first describes the different branches of the PN in detail. Subsequently, insights are provided on how therapeutic compounds directed against the different PN branches might slow down or even arrest the appalling, progressive blinding conditions. These insights are supported by findings of PN modulators in other research disciplines.

【 授权许可】

Unknown