α-Synuclein expression in substantia nigra and cortex in Parkinson's disease

Authors

  • Michael Neystat PhD,

    1. Department of Neurology, College of Physicians & Surgeons, Columbia University, Columbia-Presbyterian Medical Center, New York, NY, U.S.A.
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  • Timothy Lynch MRCPI,

    1. Department of Neurology, College of Physicians & Surgeons, Columbia University, Columbia-Presbyterian Medical Center, New York, NY, U.S.A.
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  • Serge Przedborski MD, PhD,

    1. Department of Neurology, College of Physicians & Surgeons, Columbia University, Columbia-Presbyterian Medical Center, New York, NY, U.S.A.
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  • Nikolai Kholodilov MD,

    1. Department of Neurology, College of Physicians & Surgeons, Columbia University, Columbia-Presbyterian Medical Center, New York, NY, U.S.A.
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  • Margarita Rzhetskaya,

    1. Department of Neurology, College of Physicians & Surgeons, Columbia University, Columbia-Presbyterian Medical Center, New York, NY, U.S.A.
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  • Robert E. Burke MD

    Corresponding author
    1. Department of Neurology, College of Physicians & Surgeons, Columbia University, Columbia-Presbyterian Medical Center, New York, NY, U.S.A.
    • Department of Neurology, Columbia University, Box 67, 710 W. 168th St., New York, NY 10032, U.S.A.
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Abstract

Mutations in the human α-synuclein gene have been identified in several families of European descent with early-onset Parkinson's disease (PD). We sequenced the complete α-synuclein cDNA from substantia nigra and cortex from nine patients with PD and eight control subjects. No mutations were found. We then analyzed α-synuclein mRNA levels using a ribonuclease protection assay. Two major protected bands of α-synuclein mRNA, possibly representing two splice variants of the gene, were observed. α-synuclein mRNA was significantly diminished in the substantia nigra of patients with PD compared with control subjects but not in the cortex. Our findings suggest that decreased synuclein mRNA may be an early alteration in the SN in PD, and imply that decreased levels of the protein may play a role in the pathogenesis of sporadic cases of the disease.

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