Whether inflammation is an initiating factor of PD in humans is unclear, but intracranial infusion of bacterial lipopolysaccharide (LPS), a ligand for Toll-like receptor (TLR)4 and a potent activator of microglia, is sufficient to induce the loss of TH+ neurons in rodents (Meredith et al., 2008). LPS-induced inflammation can also synergize with α-Synuclein and Parkin mutations associated with familial PD to potentiate the loss of tyrosine hydroxylase (TH)+ neurons in animal models (Frank-Cannon et al., 2008; Gao et al., 2008). These observations are consistent with the possibility that environmental factors, such as infection, may interact with common but less penetrant susceptibility genes to influence the onset of most commonly observed sporadic PD cases (Tansey et al., 2007).
