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Alpha-synuclein expression in substantia nigra and cortex in Parkinson's disease
M Neystat1, T Lynch, S Przedborski
1Department of Neurology, College of Physicians & Surgeons, Columbia University, Columbia-Presbyterian Medical Center, New York, NY 10032, USA.
Summary
Decreased alpha-synuclein messenger RNA (mRNA) levels in the substantia nigra may be an early indicator of Parkinson's disease (PD). This finding suggests reduced protein levels could contribute to sporadic PD pathogenesis.
Area of Science:
- Neuroscience
- Genetics
- Molecular Biology
Background:
- Mutations in the alpha-synuclein gene are linked to familial early-onset Parkinson's disease (PD).
- The role of alpha-synuclein in sporadic PD remains under investigation.
Purpose of the Study:
- To investigate alpha-synuclein gene mutations and mRNA levels in Parkinson's disease patients.
- To determine if altered alpha-synuclein expression is associated with Parkinson's disease.
Main Methods:
- Sequencing of alpha-synuclein cDNA from brain tissue (substantia nigra and cortex) of PD patients and controls.
- Analysis of alpha-synuclein mRNA levels using a ribonuclease protection assay.
Main Results:
- No mutations in the alpha-synuclein gene were found in the studied PD patients.
- Alpha-synuclein mRNA levels were significantly reduced in the substantia nigra of PD patients compared to controls.
- Alpha-synuclein mRNA levels were not significantly different in the cortex between PD patients and controls.
Conclusions:
- Decreased alpha-synuclein mRNA in the substantia nigra may be an early event in Parkinson's disease.
- Reduced alpha-synuclein protein levels could contribute to the pathogenesis of sporadic Parkinson's disease.