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J Neural Transm (Vienna). 2016 Apr;123(4):401-6. doi: 10.1007/s00702-016-1519-4. Epub 2016 Feb 15.

Levodopa increases oxidative stress and repulsive guidance molecule A levels: a pilot study in patients with Parkinson's disease.

Author information

1
Department of Neurology, St. Joseph Hospital Berlin-Weissensee, Gartenstr. 1, 13088, Berlin, Germany. th.mueller@alexius.de.
2
Department of Neurology, St. Josef Hospital, Ruhr University Bochum, Gudrunstrasse 56, 44791, Bochum, Germany. th.mueller@alexius.de.
3
Neuroscience Discovery Research, Global Pharmaceutical Research and Development, Abbvie Deutschland GmbH & CO KG, Knollstrasse, 67061, Ludwigshafen, Germany.
4
Department of Neurology, St. Josef Hospital, Ruhr University Bochum, Gudrunstrasse 56, 44791, Bochum, Germany.

Abstract

Exposure to free radicals influences synthesis, degradation and function of proteins, such as repulsive guidance molecule A. Decay of this protein is essential for neuronal maintenance and recovery. Levodopa elevates oxidative stress. Therefore levodopa may impact repulsive guidance molecule A metabolism. Objectives were to investigate plasma concentrations of repulsive guidance molecule A, levodopa, cysteine and cysteinyl-glycine before and 1 h after levodopa application in patients with Parkinson's disease. Cysteine and cysteinyl-glycine as biomarkers for oxidative stress exposure decreased, repulsive guidance molecule A and levodopa rose. Repulsive guidance molecule A remained unchanged in levodopa naïve patients, but particularly went up in patients on a prior chronic levodopa regimen. Decay of cysteine specifically cysteinyl-glycine results from an elevated glutathione generation with rising cysteine consumption respectively from the alternative glutathione transformation to its oxidized form glutathione disulfide after free radical scavenging. Repulsive guidance molecule A rise may inhibit physiologic mechanisms for neuronal survival.

KEYWORDS:

Cysteine; Cysteinyl-glycine; Levodopa; Oxidative stress; Parkinson’s disease; Repulsive guidance molecule A

PMID:
26880022
DOI:
10.1007/s00702-016-1519-4
[Indexed for MEDLINE]

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