title: Ubiquitin proteasome system as a pharmacological target in neurodegeneration.
abstract: Ubiquitinated protein aggregates are observed in the brains of Alzheimer's, Parkinson's and Huntington's disease patients and in other neurodegenerative disorders. These aggregates indicate that the ubiquitin proteasome system may be impaired in these diseases. To date no therapy is available that specifically targets this system, although preventing aggregate formation or stimulating the degradation of already formed aggregates by targeting components of the ubiquitin proteasome system is an attractive therapeutic approach. Here, we review the role of the ubiquitin proteasome system in aggregate formation with respect to neurodegenerative diseases, discussing the unfolded protein response, endoplasmic reticulum-associated degradation, aggresome formation and accumulation as well as aggregation and neurotoxicity of proteins involved in neurodegeneration. The potential of pharmacological intervention within this system in patients suffering from neurodegenerative diseases will be evaluated.
authors.affiliation: Netherlands Institute for Neuroscience, Research Group Cellular Quality Control, Meibergdreef 47, 1105 BA Amsterdam, The Netherlands. e.hol@nin.knaw.nl
authors.forename: Elly M
authors.initials: EM
authors.lastname: Hol
authors.forename: David F
authors.initials: DF
authors.lastname: Fischer
authors.forename: Huib
authors.initials: H
authors.lastname: Ovaa
authors.forename: Wiep
authors.initials: W
authors.lastname: Scheper
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D008959:Models, Neurological; D019636:Neurodegenerative Diseases / Q000188:drug therapy* / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D046988:Proteasome Endopeptidase Complex / Q000187:drug effects / Q000378:metabolism*; D025801:Ubiquitin / Q000378:metabolism*
chemical_list: D018696:Neuroprotective Agents; D025801:Ubiquitin; D046988:Proteasome Endopeptidase Complex