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Parkinson�s disease (PD) is one of several prevalent neurodegenerative diseases plaguing the aging population. To date,
no biological therapies have been shown to slow, stop, or reverse PD progression; the disease is considered irreversible
and progressive. The hypothesis that deficiency of reduced glutathione (GSH) contributes to PD degeneration was proposed
over thirty years ago. Advances in neuroimaging and pharmaceutical science now permit quantification of brain GSH
concentrations and novel methods of delivery, respectively. The goal of this lecture will be to present the data in evaluation of
this hypothesis and identify gaps in knowledge. Post mortem brain from individuals with premotor PD shows a deficiency of
GSH and it has been hypothesized that deficiency of GSH contributes to PD neurodegeneration. The role of GSH in the healthy
brain will be described, and evidence of GSH deficiency in PD will be reviewed. The pros and cons of various augmentation
strategies will be discussed, e.g. oral, intravenous and intranasal. All four clinical trials of GSH in PD have demonstrated a mild
symptomatic improvement. In a cross-sectional analysis of 58 individuals with PD, low blood GSH was associated with greater
disease severity. Taken together, these data support the hypothesis that GSH depletion contributes to PD and that intranasallyadministered
GSH has therapeutic potential as both a symptomatic treatment and a disease modification strategy.