In situ and in vitro study of colocalization and segregation of alpha-synuclein, ubiquitin, and lipids in Lewy bodies.
alpha-Synuclein and ubiquitin are two Lewy body protein components that may play antagonistic roles in the pathogenesis of Lewy bodies. We examined the relationship between alpha-synuclein, ubiquitin, and lipids in Lewy bodies of fixed brain sections or isolated from cortical tissues of dementia with Lewy bodies. Lewy bodies exhibited a range of labeling patterns for alpha-synuclein and ubiquitin, from a homogeneous pattern in which alpha-synuclein and ubiquitin were evenly distributed and overlapped across the inclusion body to a concentric pattern in which alpha-synuclein and ubiquitin were partially segregated, with alpha-synuclein labeling concentrated in the peripheral domain and ubiquitin in the central domain of the Lewy body. Lipids represented a significant component in both homogeneous and concentric Lewy bodies. These results suggest that Lewy bodies are heterogeneous in their subregional composition. The segregation of alpha-synuclein to Lewy body peripheral domain is consistent with the hypothesis that alpha-synuclein is continually deposited onto Lewy bodies.
Gai
W P
WP
Department of Physiology and Centre for Neuroscience, Flinders University, Bedford Park, South Australia, 5042, Australia.
Yuan
H X
HX
Li
X Q
XQ
Power
J T
JT
Blumbergs
P C
PC
Jensen
P H
PH
D000368:Aged; D000369:Aged, 80 and over; D001921:Brain / Q000473:pathology; D001923:Brain Chemistry; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D016631:Lewy Bodies / Q000737:chemistry* / Q000473:pathology / Q000648:ultrastructure; D020961:Lewy Body Disease / Q000473:pathology*; D008055:Lipids / Q000032:analysis*; D008297:Male; D016253:Microscopy, Immunoelectron; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000032:analysis*; D009474:Neurons / Q000737:chemistry / Q000473:pathology / Q000648:ultrastructure; D010300:Parkinson Disease / Q000473:pathology; D051843:Synucleins; D014452:Ubiquitins / Q000032:analysis*; D051844:alpha-Synuclein
D008055:Lipids; D009419:Nerve Tissue Proteins; C497604:SNCA protein, human; D051843:Synucleins; D014452:Ubiquitins; D051844:alpha-Synuclein