N-acetylcysteine for Parkinson’s disease: a translational systematic review of mechanistic and early clinical data

Parkinson’s disease (PD) involves progressive motor and non-motor decline, linked to oxidative stress and glutathione depletion. N-acetylcysteine (NAC), a glutathione precursor and antioxidant, is a potential disease-modifying therapy. To evaluate preclinical and clinical evidence on NAC in PD, focusing on motor and non-motor outcomes, dopaminergic function, and oxidative stress biomarkers. A PRISMA-compliant review of MEDLINE and Embase (May 2025) identified prospective studies in animal models or adults with PD. Outcomes included Unified Parkinson’s Disease Rating Scale (UPDRS), dopamine transporter (DAT) imaging, glutathione levels, and safety. Twelve studies met criteria. Preclinical models showed consistent neuroprotection. Intravenous NAC raised brain glutathione levels; high-dose oral NAC reached CSF. Two open-label trials (<i>n</i> = 65), reported ~ 13% improvement in UPDRS scores and 4–9% dopamine transporter signal increases over three months. No serious adverse events were attributed to NAC. Larger randomized controlled trials are needed to test efficacy and disease-modifying potential. Parkinson’s disease is a brain illness that gets worse over time. It causes shaking, slow movement, and trouble with daily tasks. Current drugs can ease symptoms. They do not stop brain cells from dying. One cause of cell death is oxidative stress. Harmful molecules build up. The body fights them with a shield called glutathione. People with Parkinson’s disease often have low glutathione. N-acetylcysteine, or NAC, is a safe and cost-effective medication that increases glutathione levels. Doctors use it for paracetamol overdose and for lung disease. Because NAC reduces oxidative stress, researchers are investigating whether it can protect brain cells in Parkinson’s disease. We reviewed all studies of NAC in Parkinson’s disease. In animals, NAC protected brain cells and improved movement. In small human studies, NAC has been found to reach the brain. It was safe. Some people showed slight gains in movement and on brain scans after three months. But these studies were small and not blinded. The results are not strong enough to prove a definite benefit. Larger and longer trials with placebos are needed to learn if NAC can slow the disease progression.