The united causal networks upregulated in PD brain regions included neuroprotection (WNT, PDGF and histamine H2), general neuronal functions (dopamine D2 and calcium signaling), long-term changes in neuronal function (dopamine D1A), response to stress (TNFα pathway), protein folding (heat-shock proteins), anti-oxidant defense (metallothionein family), and axonal cytoskeleton (actin and myosin) (Fig. 3a). This evidence concerns the gene TNF and Parkinson disease.