Ubiquitin-binding protein p62 is present in neuronal and glial inclusions in human tauopathies and synucleinopathies.
We examined the immunoreactivity of ubiquitin-binding protein p62 and its association with ubiquitin (Ub), alpha-synuclein, and paired helical filament (PHF)-tau in the affected brain areas of human tauopathies and synucleinopathies. Ubiquitin-binding protein p62 is a widely expressed protein that can bind to Ub noncovalently and is involved in several signalling pathways, making p62 a candidate regulator of Ub-mediated proteolysis. We show that p62 immunoreactivity co-localizes with neuronal and glial Ub-containing inclusions in Alzheimer's disease, Pick's disease, dementia with Lewy bodies, Parkinson's disease, and multiple system atrophy. This is the first demonstration of a common protein component, apart from Ub, that is present in both PHF-tau and alpha-synuclein inclusions. In both tauo- and synucleinopathies, the staining patterns for p62 and Ub were markedly similar, suggesting that a common mechanism which requires interaction of p62 and Ub contributes to the formation of PHF-tau and alpha-synuclein inclusions.
Kuusisto
E
E
1Department of Neuroscience and Neurology, Section of Neuropathology, University of Kuopio, P.O. Box 1627, FIN-70211 Kuopio, Finland.
Salminen
A
A
Alafuzoff
I
I
D048868:Adaptor Proteins, Signal Transducing; D000368:Aged; D000369:Aged, 80 and over; D001921:Brain / Q000473:pathology*; D002352:Carrier Proteins / Q000032:analysis*; D005260:Female; D006801:Humans; D017874:Immediate-Early Proteins / Q000032:analysis*; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000032:analysis*; D016501:Neurites / Q000737:chemistry / Q000473:pathology; D019636:Neurodegenerative Diseases / Q000473:pathology*; D011506:Proteins; D000071456:Sequestosome-1 Protein; D051843:Synucleins; D014452:Ubiquitins / Q000032:analysis*; D051844:alpha-Synuclein; D016875:tau Proteins / Q000032:analysis*
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D017874:Immediate-Early Proteins; D009419:Nerve Tissue Proteins; D011506:Proteins; C497604:SNCA protein, human; C099718:SQSTM1 protein, human; D000071456:Sequestosome-1 Protein; D051843:Synucleins; D014452:Ubiquitins; D051844:alpha-Synuclein; D016875:tau Proteins