Several studies have examined whether plasma and CSF zinc levels are altered in PD patients. The reported data are, however, disparate. In some studies, circulating zinc levels were lower in PD patients [
4,
5,
6,
7,
8,
9,
10,
11], while in others they were normal or even increased [
12,
13,
14,
15,
16,
17,
18]. Recent meta-analysis studies, though, point to lower zinc levels in serum and plasma and CSF of PD patients compared to healthy controls [
19,
20]. Findings from epidemiological studies examining the association of dietary intake of zinc and PD are also contradictory. Higher intake of zinc was associated with reduced risk of PD in some studies [
21], but negative findings were reported by others [
22,
23]. The association between lower levels of circulating zinc and PD has been explained by its antioxidant role since this trace element is essential for a variety of enzymes and proteins (superoxide dismutase oxidative, metallothioneins, and interleukins) involved in oxidative stress and inflammation [
24]. In support of this view, animal studies showed that exogenous zinc can produce its beneficial effects by multiple mechanisms. In vitro, zinc inhibits 6-OHDA-induced oxidative stress [
25] and reduces methamphetamine-induced dopaminergic neurotoxicity by the increasing expression of metallothioneins, which in turn prevent the generation of reactive oxygen species [
26,
27]. Zinc treatment also reduces
α-synuclein (α-syn), the predominant component of Lewy bodies, induced by methamphetamine in cell culture [
28]. Finally, zinc deficiency has been suggested to lead to dysfunction of PARK2 (E3 ligase) that possesses zinc-binding domains. PARK2 binds eight zinc ions and the removal of zinc causes a near-complete unfolding of the protein and, thereby, loss of its function [
29]. Accordingly, supplementation with zinc has been shown to increase lifespan, as well as motor function in the parkin KO Drosophila model of PD [
30].