title: ER stress in retinal degeneration: a target for rational therapy?
abstract: Mutations that cause rhodopsin misfolding and retention within the endoplasmic reticulum (ER) are a prominent cause of retinitis pigmentosa. Here, we discuss the hypothesis that the failure of photoreceptor neurons to adapt to the stress caused by rhodopsin accumulation in the ER leads to a global collapse of homeostasis and to retinal degeneration. We review the molecular mechanisms underlying the activity of local ER conformational sensors and stress-relaying modules and consider how ER-derived stress signals are amplified and implemented to impact on downstream processes, including rhodopsin clearance and cell fate control. The emerging view is that alterations to the systems responsible for the detection, transduction and implementation of ER stress might be used therapeutically to treat retinitis pigmentosa.
authors.affiliation: Department of Protein Science, Helmholtz Zentrum Munich-German Research Center for Environmental Health, Neuherberg, Germany.
authors.forename: Ana
authors.initials: A
authors.lastname: Griciuc
authors.forename: Liviu
authors.initials: L
authors.lastname: Aron
authors.forename: Marius
authors.initials: M
authors.lastname: Ueffing
mesh_terms: D000818:Animals; D004721:Endoplasmic Reticulum / Q000235:genetics / Q000378:metabolism*; D059865:Endoplasmic Reticulum Stress; D005786:Gene Expression Regulation; D006801:Humans; D058990:Molecular Targeted Therapy; D009154:Mutation / Q000235:genetics; D057165:Proteostasis Deficiencies / Q000235:genetics / Q000378:metabolism; D012162:Retinal Degeneration / Q000235:genetics / Q000378:metabolism* / Q000628:therapy*; D012174:Retinitis Pigmentosa / Q000235:genetics / Q000378:metabolism; D012243:Rhodopsin / Q000235:genetics / Q000378:metabolism; D013312:Stress, Physiological
chemical_list: D012243:Rhodopsin