title: Self-assembly of protein aggregates in ageing disorders: the lens and cataract model.
abstract: Cataract, neurodegenerative disease, macular degeneration and pathologies of ageing are often characterized by the slow progressive destabilization of proteins and their self-assembly to amyloid-like fibrils and aggregates. During normal cell differentiation, protein self-assembly is well established as a dynamic mechanism for cytoskeletal organization. With the increased emphasis on ageing disorders, there is renewed interest in small-molecule regulators of protein self-assembly. Synthetic peptides, mini-chaperones, aptamers, ATP and pantethine reportedly regulate self-assembly mechanisms involving small stress proteins, represented by human αB-crystallin, and their targets. Small molecules are being considered for direct application as molecular therapeutics to protect against amyloid and protein aggregation disorders in ageing cells and tissues in vivo. The identification of specific interactive peptide sites for effective regulation of protein self-assembly is underway using conventional and innovative technologies. The quantification of the functional interactions between small stress proteins and their targets in vivo remains a top research priority. The quantitative parameters controlling protein-protein interactions in vivo need characterization to understand the fundamental biology of self-assembling systems in normal cells and disorders of ageing.
authors.affiliation: Departments of Biological Structure and Ophthalmology, University of Washington, Seattle, WA 98195, USA. clarkji@u.washington.edu
authors.forename: John I
authors.initials: JI
authors.lastname: Clark
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D002386:Cataract / Q000378:metabolism*; D007908:Lens, Crystalline / Q000737:chemistry / Q000378:metabolism; D008954:Models, Biological; D018832:Molecular Chaperones; D010204:Pantetheine / Q000031:analogs & derivatives; D011487:Protein Conformation; D058767:Protein Unfolding; D038203:alpha-Crystallin B Chain / Q000235:genetics / Q000378:metabolism
chemical_list: D018832:Molecular Chaperones; D038203:alpha-Crystallin B Chain; D010204:Pantetheine; C005425:pantethine