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Sequential Extraction of Soluble and Insoluble Alpha-Synuclein from Parkinsonian Brains
Published on: January 5, 2016
FBXO7 immunoreactivity in α-synuclein-containing inclusions in Parkinson disease and multiple system atrophy
Tianna Zhao1, Lies-Anne Severijnen, Marcel van der Weiden
1Departments of Clinical Genetics, Erasmus MC, Rotterdam, The Netherlands.
Journal of Neuropathology and Experimental Neurology
|May 10, 2013
Summary
Mutations in the F-box only protein 7 (FBXO7) gene cause PARK15. FBXO7 protein is found in brain inclusions, suggesting its role in synucleinopathies like Parkinson disease.
Area of Science:
- Neuroscience
- Molecular Biology
- Pathology
Background:
- Mutations in F-box only protein 7 (FBXO7) cause PARK15, a rare form of juvenile parkinsonism.
- FBXO7's role in brain pathology and its expression in neurodegenerative diseases are poorly understood.
- Understanding FBXO7 may illuminate mechanisms of dopaminergic neuron degeneration relevant to Parkinson disease.
Purpose of the Study:
- To characterize FBXO7 protein expression in the human brain.
- To investigate FBXO7 expression in Parkinson disease (PD), multiple system atrophy (MSA), Alzheimer disease (AD), and progressive supranuclear palsy (PSP).
- To determine if FBXO7 is associated with protein aggregates in these neurodegenerative conditions.
Main Methods:
- Immunohistochemistry was used to detect FBXO7 protein in post-mortem brain samples.
- Samples included normal controls, PD, MSA, AD, and PSP cases.
- Two anti-FBXO7 antibodies were employed for detection and colocalization studies.
Main Results:
- Widespread FBXO7 immunoreactivity was observed in the brain, particularly in neurons of the cortex, putamen, and cerebellum.
- No significant differences in overall FBXO7 expression were found between normal and PD brains.
- FBXO7 colocalized with α-synuclein in Lewy bodies, Lewy neurites, and glial cytoplasmic inclusions in PD and MSA, but showed weak association with tau in AD and PSP.
Conclusions:
- FBXO7 is widely expressed in the human brain, with notable presence in neurons.
- FBXO7 is a component of α-synuclein aggregates in synucleinopathies (PD and MSA).
- These findings suggest a potential role for FBXO7 in the pathogenesis of synucleinopathies.
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