Protein aggregation and the ubiquitin proteasome pathway: gaining the UPPer hand on neurodegeneration.
Protein misfolding and aggregation are common to most neurodegenerative diseases, suggesting that abnormalities of protein homeostasis contribute to pathogenesis. Research implicates at least two components of cellular protein quality control in disease: molecular chaperones and the ubiquitin-proteasome pathway (UPP). Although evidence is more compelling for chaperone involvement, recent cell-based and genetic studies suggest that perturbations in the UPP also contribute to neurodegenerative disease processes. UPP involvement in disease seems even more probable when the UPP is viewed not simply as an isolated degradation machine but rather as a complex cascade linked both to other ubiquitin-dependent processes and to chaperone systems.
Berke
Sarah J Shoesmith
SJ
Department of Neurology and Neuroscience Graduate Program, Paulson Laboratory - 240 EMRB, University of Iowa, Iowa City, Iowa 52242, USA. sarah-berke@uiowa.edu
Paulson
Henry L
HL
D003546:Cysteine Endopeptidases / Q000378:metabolism*; D006801:Humans; D018832:Molecular Chaperones / Q000378:metabolism; D009097:Multienzyme Complexes / Q000378:metabolism*; D019636:Neurodegenerative Diseases / Q000378:metabolism* / Q000628:therapy; D046988:Proteasome Endopeptidase Complex; D017510:Protein Folding; D025801:Ubiquitin / Q000378:metabolism*
D018832:Molecular Chaperones; D009097:Multienzyme Complexes; D025801:Ubiquitin; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex