title: Cystatin C in macular and neuronal degenerations: implications for mechanism(s) of age-related macular degeneration.
abstract: Cystatin C is a strong inhibitor of cysteine proteinases expressed by diverse cells. Variant B cystatin C, which was associated with increased risk of developing age-related macular degeneration, differs from the wild type protein by a single amino acid (A25T) in the signal sequence responsible for its targeting to the secretory pathway. The same variant conveys susceptibility to Alzheimer disease. Our investigations of the trafficking and processing of variant B cystatin C in living RPE cells highlight impaired secretion of extracellular modulators and inappropriate protein retention in RPE cells as potential molecular mechanisms underpinning macular, and possibly neuronal, degeneration.
authors.affiliation: Unit of Ophthalmology, School of Clinical Sciences, Liverpool L69 3GA, UK. luminita.paraoan@liverpool.ac.uk
authors.forename: Luminita
authors.initials: L
authors.lastname: Paraoan
authors.forename: Paul
authors.initials: P
authors.lastname: Hiscott
authors.forename: Christine
authors.initials: C
authors.lastname: Gosden
authors.forename: Ian
authors.initials: I
authors.lastname: Grierson
mesh_terms: D055316:Cystatin C / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D005123:Eye / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008268:Macular Degeneration / Q000276:immunology / Q000378:metabolism*; D010857:Pigment Epithelium of Eye / Q000378:metabolism*; D055351:Retinal Neurons / Q000378:metabolism
chemical_list: D055316:Cystatin C