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Human Peripheral Blood Neutrophil Isolation for Interrogating the Parkinson's Associated LRRK2 Kinase Pathway by Assessing Rab10 Phosphorylation
Published on: March 21, 2020
LRRK2 and parkin immunoreactivity in multiple system atrophy inclusions
Yue Huang1, Yun Ju Christine Song, Karen Murphy
1Prince of Wales Medical Research Institute, Barker Street, Randwick, NSW, 2031, Australia.
Acta Neuropathologica
|October 22, 2008
Summary
LRRK2 protein is found in most abnormal brain cells in multiple system atrophy (MSA), suggesting its early role in disease initiation. Reduced LRRK2 levels correlate with greater neuronal loss in MSA patients.
Area of Science:
- Neuroscience
- Cell Biology
- Pathology
Background:
- Genetic defects in LRRK2 and parkin are linked to Parkinson's disease (PD) and Lewy body formation.
- LRRK2 is implicated in the early stages of Lewy body development.
- The role of LRRK2 and parkin in alpha-synuclein deposition in multiple system atrophy (MSA) glial cytoplasmic inclusions (GCI) is not well understood.
Purpose of the Study:
- To investigate the association of LRRK2 and parkin with abnormal alpha-synuclein deposition in MSA GCI.
- To determine if LRRK2 and parkin exhibit similar deposition patterns in MSA as observed in PD.
Main Methods:
- Immunohistochemistry was used on brain tissue from 12 MSA patients, 4 PD patients, and 4 controls.
- Triple labeling procedures identified LRRK2, parkin, alpha-synuclein, and oligodendroglial proteins.
- Neuronal loss severity and protein co-localization in enlarged oligodendroglia were quantified.
Main Results:
- Parkin was found in a small subset of GCI.
- LRRK2 was present in most enlarged oligodendroglia in MSA and co-localized with alpha-synuclein in GCI.
- LRRK2 immunoreactivity was observed in degrading myelin, an early MSA abnormality.
- Increased LRRK2-positive GCI correlated with decreased neuronal loss and alpha-synuclein-positive dystrophic axons.
Conclusions:
- LRRK2 expression increases early in MSA, associated with myelin degradation and GCI formation.
- Reduced LRRK2 expression in oligodendroglia is linked to increased neuronal loss in MSA.
- LRRK2 plays a significant role in the early pathogenesis of MSA.
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