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Involvement of 4-hydroxy-2-nonenal accumulation in multiple system atrophy
Noriyuki Shibata1, Yuri Inose, Sono Toi
1Department of Pathology, Tokyo Women's Medical University, Tokyo, Japan. shibatan@research.twmu.ac.jp
Acta Histochemica Et Cytochemica
|June 2, 2010
Summary
Lipid peroxidation, indicated by protein-bound 4-hydroxy-2-nonenal (P-HNE), is accelerated in multiple system atrophy (MSA). This suggests HNE contributes to alpha-synuclein-induced neuroinflammation and cytotoxicity in MSA patients.
Area of Science:
- Neuroscience
- Pathology
- Biochemistry
Background:
- Alpha-synuclein (α-synuclein) cytotoxicity is implicated in the pathology of multiple system atrophy (MSA).
- In vitro studies suggest α-synuclein generates oxidative stress, potentially accelerating lipid peroxidation in MSA.
Purpose of the Study:
- To investigate the role of lipid peroxidation in MSA pathogenesis.
- To determine if protein-bound 4-hydroxy-2-nonenal (P-HNE) is elevated in MSA brain tissue.
Main Methods:
- Immunohistochemical analysis of P-HNE in archival pontine tissue from eight sporadic MSA patients and eight age-matched controls.
- Identification of inclusions using α-synuclein and ubiquitin markers.
Main Results:
- P-HNE immunoreactivity was detected in neuronal and glial cytoplasmic inclusions containing α-synuclein and ubiquitin in MSA cases.
- P-HNE was also found in reactive astrocytes and phagocytic microglia but not activated microglia in MSA.
- Control cases showed minimal or no P-HNE immunoreactivity in the brain parenchyma.
Conclusions:
- These findings provide in vivo evidence that 4-hydroxy-2-nonenal (HNE) is involved in α-synuclein-induced cytotoxicity in MSA.
- HNE appears to play a role in the neuroinflammatory processes occurring in multiple system atrophy.
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