Proteostasis is age‐related macular degeneration

Abstract

AbstractThe accumulation of damaged and harmful components in cells, particularly those composed of misfolded and potentially hazardous proteins, is characteristic for several neurodegenerative diseases, including age‐related macular degeneration (AMD). Misfolded proteins frequently expose hydrophobic patches that structurally should be buried inside the protein, making the misfolded proteins prone to aggregation. Inefficient protein homeostasis and failures in removing misfolded and aggregated proteins or impaired organelles, especially damaged mitochondria, can lead to the production of reactive oxygen species and increase in oxidative stress. Oxidative stress‐induced damage to the retinal pigment epithelium (RPE) is considered to be a key factor in AMD pathology. The ubiquitin‐proteasome and the lysosomal/autophagy pathways are the two major proteolytic systems to remove damaged proteins and organelles. There is increasing evidence that proteostasis is disturbed in RPE as evidenced by lysosomal lipofuscin and extracellular drusen accumulation in AMD. The role of clearance mechanisms in AMD pathology will be discussed.