title: Cerebrospinal fluid concentrations of N-acetylcysteine after oral administration in Parkinson's disease.
abstract: BACKGROUND
  Depletion of neuronal glutathione may contribute to the pathogenesis of Parkinson's disease (PD). N-acetylcysteine (NAC) can restore neuronal glutathione levels, but it has not been established whether NAC can cross the blood-brain barrier in humans.
  
  
  METHODS
  Twelve patients with PD were given oral NAC twice daily for 2 days. Three doses were compared: 7 mg/kg, 35 mg/kg, and 70 mg/kg. NAC, cysteine, and glutathione were measured in the cerebrospinal fluid (CSF) at baseline and 90 min after the last dose. Cognitive and motor functions were assessed pre- and post-NAC administration using the Montreal Cognitive Assessment (MoCA) and the Unified Parkinson's Disease Rating Scale part III motor subscore (UPDRS-III).
  
  
  RESULTS
  Oral NAC produced a dose-dependent increase in CSF NAC concentrations (p < 0.001), with the highest dose producing a CSF concentration of 9.26 ± 1.62 μM. There were no significant adverse events. NAC had no acute effect on motor or cognitive function.
  
  
  CONCLUSIONS
  Orally administered NAC produces biologically relevant CSF NAC concentrations at doses that are well tolerated. The findings support the feasibility of NAC as a potential disease-modifying therapy for PD.
authors.affiliation: Neurology Service, San Francisco Veterans Affairs Medical Center, 4150 Clement Street, San Francisco, CA 94121, USA; Department of Neurology, University of California, San Francisco Medical Center, 675 Nelson Rising Lane, San Francisco, CA 94143, USA. Electronic address: maya.katz@ucsfmedctr.org.
authors.forename: Maya
authors.initials: M
authors.lastname: Katz
authors.affiliation: Neurology Service, San Francisco Veterans Affairs Medical Center, 4150 Clement Street, San Francisco, CA 94121, USA; Department of Neurology, University of California, San Francisco Medical Center, 675 Nelson Rising Lane, San Francisco, CA 94143, USA.
authors.forename: Seok Joon
authors.initials: SJ
authors.lastname: Won
authors.affiliation: Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, Emory University, 615 Michael Street, Suite 205, Atlanta, GA 30322, USA.
authors.forename: Youngja
authors.initials: Y
authors.lastname: Park
authors.affiliation: Neurology Service, San Francisco Veterans Affairs Medical Center, 4150 Clement Street, San Francisco, CA 94121, USA; Department of Neurology, University of California, San Francisco Medical Center, 675 Nelson Rising Lane, San Francisco, CA 94143, USA.
authors.forename: Adrienne
authors.initials: A
authors.lastname: Orr
authors.affiliation: Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, Emory University, 615 Michael Street, Suite 205, Atlanta, GA 30322, USA.
authors.forename: Dean P
authors.initials: DP
authors.lastname: Jones
authors.affiliation: Neurology Service, San Francisco Veterans Affairs Medical Center, 4150 Clement Street, San Francisco, CA 94121, USA; Department of Neurology, University of California, San Francisco Medical Center, 675 Nelson Rising Lane, San Francisco, CA 94143, USA.
authors.forename: Raymond A
authors.initials: RA
authors.lastname: Swanson
authors.affiliation: Neurology Service, San Francisco Veterans Affairs Medical Center, 4150 Clement Street, San Francisco, CA 94121, USA; Department of Neurology, University of California, San Francisco Medical Center, 675 Nelson Rising Lane, San Francisco, CA 94143, USA.
authors.forename: Graham A
authors.initials: GA
authors.lastname: Glass
mesh_terms: D000111:Acetylcysteine / Q000008:administration & dosage* / Q000134:cerebrospinal fluid*; D000284:Administration, Oral; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000134:cerebrospinal fluid; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000134:cerebrospinal fluid* / Q000188:drug therapy*
chemical_list: D015415:Biomarkers; D000111:Acetylcysteine
keywords: Cysteine; Glutathione; Neuroprotection; Parkinson's disease; Therapeutics