title: Polyglutamine diseases and transport problems: deadly traffic jams on neuronal highways.
abstract: The expansion of CAG repeats encoding glutamine (polyQ) causes, to date, 9 late-onset progressive neurodegenerative disorders, including Huntington disease, spinobulbar muscular atrophy, dentatorubral-pallidoluysian atrophy, and spinocerebellar ataxias 1, 2, 3, 6, 7, and 17. Although many studies using both knockout and transgenic mouse models suggest that a toxic gain of function is central to neuronal dysfunction, the exact mechanisms of neurotoxic effects remain elusive. Protein aggregations within neurons seem to be a common manifestation in almost all polyQ diseases, and such accumulations are perhaps major triggers of cellular stress and neuronal death. Recent data lead to the tantalizing proposal that disruption of axonal transport pathways within long, narrow-caliber axons could lead to protein accumulations that can elicit neuronal death, ultimately causing a neuronal dysfunction pathway observed in polyQ expanded diseases. Perhaps perturbations in transport pathways are an early event involved in instigating polyQ disease pathology.
authors.affiliation: Howard Hughes Medical Institute, Department of Cellular and Molecular Medicine, School of Medicine, University of California-San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0683, USA.
authors.forename: Shermali
authors.initials: S
authors.lastname: Gunawardena
authors.forename: Lawrence S B
authors.initials: LS
authors.lastname: Goldstein
mesh_terms: D000818:Animals; D001370:Axonal Transport / Q000235:genetics*; D020271:Heredodegenerative Disorders, Nervous System / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D008870:Microtubules / Q000502:physiology; D008954:Models, Biological; D020258:Neurotoxicity Syndromes / Q000503:physiopathology; D010455:Peptides / Q000235:genetics*; D019680:Trinucleotide Repeat Expansion / Q000235:genetics
chemical_list: D010455:Peptides; C097188:polyglutamine