Parkinson's disease signalling pathways traced out by susceptibility genes

As with many other polygenic diseases, the genes implicated in Parkinson's disease trace out sets of pathways that relate to each other, and to the risk factors implicated in the disease. A Kegg pathway analysis of the genes implicated in Parkinson's disease is shown on this post. Mitochondrial and oxidative phosphorylation genes can evidently be related to the mitochondrial toxins, MPTP , rotenone and paraquat , and cytochrome p450 and xenobiotic metabolism genes can also be related to environmental toxins. Generic pathogen entry pathways relate to viruses and pathogens that have been implicated as risk factors (influenza, coronavirus Herpes simplex. T.Gondii and Helicobacter  pylori).  Chemokine, cytokine and T-cell pathways related to the immune system could also be considered in terms of pathogen defence, as can Toll receptor, NOD and RIG pathways.  (see risk factor database)

Living in a rural environment and the use of pesticides have been implicated as environmental risk factors.
Clearly, not everyone in this situation develops Parkinson's disease, but they may do so if the p450 and other metabolism related genes are less able to deal with these toxins, or if the mitochondrial genes render the mitochondrial proteins more sensitive to their effects.
 
Genes and risk factors likely work together via these and other pathways. GWAS will no doubt unearth more genes, but those already existing, together with the environmental risk factors tell a story that is highly relevant to our understanding of Parkinson's disease. GWAS studies, because of the large numbers used, may iron out these environmental interactions, but partitioning the data in relation to environmental effects may be informative.

These maps are from the Kegg pathway database , under the conditions of an academic licence, with thanks.

Other pathways