Cerebrospinal fluid concentrations of N-acetylcysteine after oral administration in Parkinson's disease

Parkinsonism & Related Disorders
Maya KatzGraham A Glass

Abstract

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. 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). 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. 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.

References

Feb 1, 1989·Journal of Neurochemistry·P RiedererM B Youdim
Nov 15, 2008·Journal of Pharmacological Sciences·Koji AoyamaToshio Nakaki
Mar 30, 2011·Annals of Neurology·Ari E BermanRaymond A Swanson
May 2, 2012·Medical Hypotheses·Marcos Arturo Martínez-Banaclocha
Feb 2, 2013·Trends in Pharmacological Sciences·Michael BerkOlivia M Dean
Apr 27, 2013·Biochimica Et Biophysica Acta·Yuval SamuniMichael Berk
May 15, 2013·Free Radical Biology & Medicine·Michelle Smeyne, Richard Jay Smeyne
Jul 19, 2013·Clinical Neuropharmacology·Mary J HolmayPaul J Tuite

❮ Previous
Next ❯

Citations

Nov 18, 2015·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Reno C ReyesRaymond A Swanson
Mar 1, 2016·Free Radical Biology & Medicine·Narciso CoutoJill Barber
Aug 2, 2016·Movement Disorders : Official Journal of the Movement Disorder Society·Sara C LaHueCaroline M Tanner
Dec 6, 2017·International Journal of Molecular Sciences·Dhyanesh PatelGeorge Henderson
Oct 21, 2017·Journal of Child and Adolescent Psychopharmacology·Kathryn R CullenLynn E Eberly
Aug 26, 2018·The European Journal of Neuroscience·Jacqueline S WomersleyJoachim D Uys
Aug 24, 2017·Molecular Pharmacology·Amanda M GleixnerRehana K Leak
Feb 25, 2016·NPJ Parkinson's Disease·Laurie K MischleyJeannie M Padowski
Dec 5, 2019·Southern Medical Journal·Christine C FergusonAmy C Ellis
Aug 25, 2020·Oxidative Medicine and Cellular Longevity·Alejandra Guillermina Miranda-DíazErnesto Germán Cardona-Muñoz
Dec 18, 2020·Journal of Biomedical Materials Research. Part B, Applied Biomaterials·Saja Al-SaloumCarolyn A Harris
Mar 7, 2021·Annals of Clinical and Translational Neurology·Kristen M KryskoEmmanuelle Waubant
Jun 18, 2017·Experimental Neurology·Grace F CrottyMichael A Schwarzschild
Mar 25, 2021·Nature Communications·Michael E MarchHakon Hakonarson
Apr 4, 2021·Antioxidants·Ana Patricia Duarte-JuradoHumberto Rodriguez-Rocha
Jul 12, 2020·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Geir BjørklundMichael Maes

❮ Previous
Next ❯

Related Concepts

Related Feeds

Blood Brain Barrier Chips

The blood brain barrier (BBB) is comprised of endothelial cells that regulate the influx and outflux of plasma concentrations. Lab-on-a-chip devices allow scientists to model diseases and mechanisms such as the passage of therapeutic antibodies across the BBB. Discover the latest research on BBB chips here.

CSF & Lymphatic System

This feed focuses on Cerebral Spinal Fluid (CSF) and the lymphatic system. Discover the latest papers using imaging techniques to track CSF outflow into the lymphatic system in animal models.

Blood Brain Barrier

The blood brain barrier is a border that separates blood from cerebrospinal fluid. Discover the latest search on this highly selective semipermeable membrane here.