Polyglutamines placed into context.
Nine inherited neurodegenerative disorders result from polyglutamine expansions. Two recently published papers on spinocerebellar ataxia type 1, together with studies on spinobulbar muscular atrophy last year, indicate that host protein context is the key arbiter of polyglutamine disease protein toxicity. This insight may represent the most important development in the field since the recognition of nuclear inclusions or the propensity of polyglutamine to aggregate. Indeed, an intimate and inextricable relationship may exist between polyglutamine neurotoxicity and the normal interactions, domains, modifications, and functions of the respective disease proteins.
La Spada
Albert R
AR
Department of Laboratory Medicine, Division of Medical Genetics (Medicine) University of Washington Medical Center, Seattle, WA 98195, USA. laspada@u.washington.edu
Taylor
J Paul
JP
D048948:14-3-3 Proteins; D000818:Animals; D016923:Cell Death / Q000235:genetics*; D002531:Cerebellum / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D010455:Peptides / Q000235:genetics / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases; D017434:Protein Structure, Tertiary / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D020754:Spinocerebellar Ataxias / Q000235:genetics / Q000378:metabolism*; D019680:Trinucleotide Repeat Expansion / Q000235:genetics*; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics / Q000378:metabolism
D048948:14-3-3 Proteins; D010455:Peptides; D011518:Proto-Oncogene Proteins; C097188:polyglutamine; D014446:Tyrosine 3-Monooxygenase; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt