title: Levodopa increases oxidative stress and repulsive guidance molecule A levels: a pilot study in patients with Parkinson's disease.
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.
authors.affiliation: Department of Neurology, St. Joseph Hospital Berlin-Weissensee, Gartenstr. 1, 13088, Berlin, Germany. th.mueller@alexius.de.|Department of Neurology, St. Josef Hospital, Ruhr University Bochum, Gudrunstrasse 56, 44791, Bochum, Germany. th.mueller@alexius.de.
authors.forename: Thomas
authors.initials: T
authors.lastname: Müller
authors.affiliation: Neuroscience Discovery Research, Global Pharmaceutical Research and Development, Abbvie Deutschland GmbH & CO KG, Knollstrasse, 67061, Ludwigshafen, Germany.
authors.forename: Isabel
authors.initials: I
authors.lastname: Trommer
authors.affiliation: Department of Neurology, St. Josef Hospital, Ruhr University Bochum, Gudrunstrasse 56, 44791, Bochum, Germany.
authors.forename: Siegfried
authors.initials: S
authors.lastname: Muhlack
authors.affiliation: Neuroscience Discovery Research, Global Pharmaceutical Research and Development, Abbvie Deutschland GmbH & CO KG, Knollstrasse, 67061, Ludwigshafen, Germany.
authors.forename: Bernhard K
authors.initials: BK
authors.lastname: Mueller
mesh_terms: D000368:Aged; D000978:Antiparkinson Agents / Q000097:blood / Q000627:therapeutic use; D002230:Carbidopa / Q000009:adverse effects*; D002851:Chromatography, High Pressure Liquid; D003545:Cysteine / Q000097:blood; D004151:Dipeptides / Q000097:blood; D004338:Drug Combinations; D005260:Female; D058851:GPI-Linked Proteins / Q000097:blood; D006801:Humans; D007980:Levodopa / Q000009:adverse effects / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000097:blood*; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D010300:Parkinson Disease / Q000188:drug therapy* / Q000378:metabolism*; D010865:Pilot Projects
chemical_list: D000978:Antiparkinson Agents; D004151:Dipeptides; D004338:Drug Combinations; D058851:GPI-Linked Proteins; D009419:Nerve Tissue Proteins; C522183:RGMA protein, human; C009265:carbidopa, levodopa drug combination; C028505:cysteinylglycine; D007980:Levodopa; D003545:Cysteine; D002230:Carbidopa
keywords: Cysteine; Cysteinyl-glycine; Levodopa; Oxidative stress; Parkinson’s disease; Repulsive guidance molecule A