Biomaterial Database

Balancing the Photoreceptor Proteome: Proteostasis Network Therapeutics for Inherited Retinal Disease. 2019

Siebren Faber, and Ronald Roepman

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

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.

UI	MeSH Term	Description	Entries
D012164	Retinal Diseases	Diseases involving the RETINA.	Disease, Retinal,Diseases, Retinal,Retinal Disease
D004791	Enzyme Inhibitors	Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.	Enzyme Inhibitor,Inhibitor, Enzyme,Inhibitors, Enzyme
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000072661	Ciliopathies	Genetic disorders caused by defects in genes related to the primary CILIUM; BASAL BODY; or CENTROSOME. Primary features may include obesity, SKELETAL DYSPLASIA; POLYDACTYLY and malformations that primarily involve the liver, eye or kidneys.	Ciliopathy
D000074702	Proteostasis	Regulation of the concentration, folding, interactions, and cellular localization of each of the proteins that comprise the PROTEOME.	Protein Homeostasis,Homeostases, Protein,Homeostasis, Protein,Protein Homeostases,Proteostases
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D020419	Photoreceptor Cells, Vertebrate	Specialized PHOTOTRANSDUCTION neurons in the vertebrates, such as the RETINAL ROD CELLS and the RETINAL CONE CELLS. Non-visual photoreceptor neurons have been reported in the deep brain, the PINEAL GLAND and organs of the circadian system.	Retinal Photoreceptor Cells,Rods and Cones,Photoreceptors, Retinal,Photoreceptors, Vertebrate,Retinal Photoreceptors,Vertebrate Photoreceptor Cells,Vertebrate Photoreceptors,Cell, Retinal Photoreceptor,Cell, Vertebrate Photoreceptor,Cells, Retinal Photoreceptor,Cells, Vertebrate Photoreceptor,Cones and Rods,Photoreceptor Cell, Retinal,Photoreceptor Cell, Vertebrate,Photoreceptor Cells, Retinal,Photoreceptor, Retinal,Photoreceptor, Vertebrate,Retinal Photoreceptor,Retinal Photoreceptor Cell,Vertebrate Photoreceptor,Vertebrate Photoreceptor Cell
D020543	Proteome	The protein complement of an organism coded for by its genome.	Proteomes