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Alteration in alpha-synuclein mRNA expression in Parkinson's disease
Ann E Kingsbury1, Susan E Daniel, Hardev Sangha
1Queen Square Brain Bank for Neurological Disorders, Institute of Neurology, London, United Kingdom.
Movement Disorders : Official Journal of the Movement Disorder Society
|February 24, 2004
Summary
Alpha-synuclein mRNA expression is widespread in the brain, but significantly reduced in key Parkinson's disease (PD) areas. This suggests Lewy body formation in PD is unlikely due to gene overexpression.
Area of Science:
- Neuroscience
- Genetics
- Pathophysiology
Background:
- Alpha-synuclein is a presynaptic protein implicated in Parkinson's disease (PD) pathophysiology.
- Point mutations in the alpha-synuclein gene are linked to familial PD, and alpha-synuclein forms Lewy bodies, the hallmark of sporadic PD.
- The relationship between abnormal alpha-synuclein accumulation and gene expression levels in neurodegeneration remains unclear.
Purpose of the Study:
- To investigate alpha-synuclein gene expression in control and Parkinson's disease (PD) brains.
- To determine if abnormal alpha-synuclein accumulation in PD results from altered gene expression.
- To explore the correlation between alpha-synuclein mRNA levels and Lewy body formation.
Main Methods:
- Semiquantitative in situ hybridization was employed to study alpha-synuclein mRNA expression.
- Analysis was conducted on brain tissue from control subjects and individuals with Parkinson's disease.
- Expression levels were compared across various brain regions, including cortical areas, hippocampus, cerebellum, brain stem, and striatum.
Main Results:
- Alpha-synuclein mRNA was widely expressed in neurons across most cortical regions, hippocampus, cerebellum, and brain stem, with minimal expression in the striatum and no signal in glia.
- High neuronal expression did not correlate with Lewy body presence, observed in both susceptible and less susceptible regions.
- Significantly reduced alpha-synuclein mRNA expression was found in melanized substantia nigra neurons and frontal cortex neurons in PD brains, with a negative correlation to disease duration in substantia nigra neurons.
Conclusions:
- Alpha-synuclein mRNA expression is broadly distributed in the human brain.
- The findings suggest that Lewy body formation in Parkinson's disease is unlikely to be caused by alpha-synuclein gene overexpression.
- Reduced alpha-synuclein mRNA expression in specific neuronal populations may be associated with Parkinson's disease progression.