title: Kaleidoscopic protein-protein interactions in the life and death of ataxin-1: new strategies against protein aggregation.
abstract: Understanding how proteins protect themselves from aberrant aggregation is of primary interest for understanding basic biology, protein biochemistry, and human disease. We discuss the paradigmatic example of ataxin-1 (Atx1), the protein responsible for neurodegenerative spinocerebellar ataxia type 1 (SCA1). This disease is part of the increasing family of pathologies caused by protein aggregation and misfolding. We discuss the importance of protein-protein interactions not only in the nonpathological function of Atx1 but also in protecting the protein from aggregation and misfolding. The lessons learned from Atx1 may lead to a more general understanding of the cell's protective strategies against aggregation. The obtained knowledge may suggest a new perspective for designing specific therapeutic strategies for the cure of misfolding diseases.
authors.affiliation: National Institute for Medical Research (NIMR), Medical Research Council (MRC), The Ridgeway, London NW7 1AA, UK.
authors.forename: Cesira
authors.initials: C
authors.lastname: de Chiara
authors.affiliation: Department of Clinical Neurosciences, King's College London, Denmark Hill Campus, London, UK. Electronic address: apastor@nimr.mrc.ac.uk.
authors.forename: Annalisa
authors.initials: A
authors.lastname: Pastore
mesh_terms: D000818:Animals; D000067696:Ataxin-1; D000067528:Ataxins; D042622:DNA Repeat Expansion; D015195:Drug Design; D020271:Heredodegenerative Disorders, Nervous System / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D006801:Humans; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D010455:Peptides / Q000235:genetics / Q000378:metabolism; D066329:Protein Aggregates; D066263:Protein Aggregation, Pathological; D017510:Protein Folding; D055503:Protein Multimerization
chemical_list: C000593749:ATXN1 protein, human; D000067696:Ataxin-1; D000067528:Ataxins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D010455:Peptides; D066329:Protein Aggregates; C097188:polyglutamine
keywords: misfolding diseases; polyglutamine; protein aggregation; protein–protein interactions