The proteasome in Alzheimer's disease and Parkinson's disease: lessons from ubiquitin B+1.
Ubiquitin-containing cellular inclusions are characteristic of major neurodegenerative diseases and suggest an involvement of the ubiquitin-proteasome system. The frameshifted form of ubiquitin has proved to be a valuable tool for studying the role of the ubiquitin-proteasome system. It is an endogenous reporter for proteasome activity in human pathology but it is also capable of inhibiting proteasomal degradation. Current studies have revealed that the frameshifted form of ubiquitin accumulates in the brains of patients with Alzheimer's disease but not in those with Parkinson's disease.
Hol
Elly M
EM
Research group Cellular Quality Control, The Netherlands Institute for Brain Research, Meibergdreef 33, 1105 AZ Amsterdam, The Netherlands. e.hol@nih.knaw.nl
van Leeuwen
Fred W
FW
Fischer
David F
DF
D000544:Alzheimer Disease / Q000378:metabolism*; D016368:Frameshift Mutation / Q000235:genetics*; D017930:Genes, Reporter / Q000235:genetics*; D006801:Humans; D002479:Inclusion Bodies / Q000378:metabolism / Q000473:pathology; D008954:Models, Biological; D010300:Parkinson Disease / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D025801:Ubiquitin / Q000235:genetics / Q000378:metabolism*
C479419:UBB protein, human; D025801:Ubiquitin; D046988:Proteasome Endopeptidase Complex