In Situ and in Vitro Study of Colocalization and Segregation of α-Synuclein, Ubiquitin, and Lipids in Lewy Bodies
Abstract
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.
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Impaired 26S proteasomal function causes neurodegeneration and intraneuronal inclusion body formation, reflecting early forms of human Lewy bodies described as homogeneous Lewy bodies or pale bodies.
“Impaired 26S proteasomal function causes neurodegeneration and intraneuronal inclusion body formation, reflecting early forms of human Lewy bodies described as homogeneous Lewy bodies (Gai et al., 2000) or pale bodies (Dale et al., 1992).”
From Depletion of 26S Proteasomes in Mouse Brain Neurons Causes Neurodegeneration and Lewy-Like Inclusions Resembling Human Pale Bodies (2008) · cites this paper as Gai et al., 2000
The pattern of α-synuclein aggregate in the mouse model, containing mitochondria, has been recognized in human disease and is considered to be an early form of Lewy body.
“The pattern of ␣-synuclein aggregate in our model, containing mitochondria, has been recognized in human disease and is considered to be an early form of Lewy body”
From Depletion of 26S Proteasomes in Mouse Brain Neurons Causes Neurodegeneration and Lewy-Like Inclusions Resembling Human Pale Bodies (2008) · cites this paper as Gai et al., 2000
Electron microscopic analysis by Gai et al. revealed that many mitochondria are concentrated in the early forms of LBs.
“Electron microscopic analysis by Gai et al. revealed that many mitochondria are concentrated in the early forms of LBs25”
From Loss of autophagy in dopaminergic neurons causes Lewy pathology and motor dysfunction in aged mice (2018) · cites this paper as [25]
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BackgroundProteasomal Inhibition by α-Synuclein Filaments and Oligomers
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“Mitochondrial involvement in inclusion body formation The pattern of -synuclein aggregate in our model, containing mitochondria, has been recognized in human disease and is considered to be an early form of Lewy body (Gai et al., 2000).”
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- Authors
- Gai, W. P., Yuan, H. X., Li, X. Q., Power, J. T. H., Blumbergs, P. C., & Jensen, P. H.
- Affiliations
- Flinders University (AU)
- The University of Melbourne (AU)
- South Australia Pathology (AU)
- Aarhus University (DK)
- Venue
- Experimental Neurology
- Publisher
- Elsevier BV
- Published
- 2000-12
- Volume
- 166
- Issue
- 2
- Pages
- 324-333
- ISSN
- 0014-4886 (ISSN-L)
- OpenAlex
- W1979147091
- Cited by
- 272
- References
- 50
- Citations by year
- 2026: 4 · 2025: 19 · 2024: 11 · 2023: 10 · 2022: 15 · 2021: 9 · 2020: 9 · 2019: 8 · 2018: 11 · 2017: 4 · 2016: 7 · 2015: 15 · 2014: 4 · 2013: 9 · 2012: 9
- FWCI
- 6.99
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Experimental Neurology (publishedVersion)
- PubMed (publishedVersion)
- Adelaide Research & Scholarship (AR&S) (University of Adelaide) (submittedVersion)
- Funders
- National Health and Medical Research Council
- National Medical Research Council
- Topics
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- alpha-synuclein, ubiquitin, Lewy bodies, dementia with Lewy bodies, protein segregation, protein deposition, Parkinson's disease
- MeSH terms
- Aged, Aged, 80 and over, Brain, Brain Chemistry, Female, Humans, Lipids, Male, Middle Aged, Nerve Tissue Proteins, Neurons, Parkinson Disease, Ubiquitins, Microscopy, Immunoelectron, Lewy Bodies, Lewy Body Disease, Synucleins, alpha-Synuclein, In Vitro Techniques
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