Convergence of signalling pathways in innate immune responses and genetic forms of Parkinson's disease

In recent years progress in molecular biology and genetics have advanced our understanding of neurological disorders and highlighted synergistic relationships with inflammatory and age-related processes. Parkinson's disease (PD) is a common neurodegenerative disorder that is characterized by loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc). Increasing extensive evidence supports the contribution of genetic risk variants and inflammation in the pathobiology of this disease. Functional and genetic studies demonstrate an overlap between genes linked to increased risk for PD and autoimmune diseases. Variants identified in loci adjacent to LRRK2, GBA, and HLA establish a crosstalk between the pathobiologies of the two disease spectra. Furthermore, common signalling pathways associated with the pathogenesis of genetic PD are also relevant to inflammatory signaling include MAPK, NF-kappa B, Wnt and inflammasome signaling. Importantly, post-mortem analyses of brain and cerebrospinal fluid from PD patients show the accumulation of proinflammatory cytokines. In this review we will focus on the principal mechanisms of genetic, inflammatory and age-related risk that intersect in the pathogenesis of PD.

Automated summary

Recent progress in molecular biology and genetics has advanced our understanding of the pathogenesis of Parkinson's disease (PD), highlighting synergistic relationships with inflammatory and age-related processes. Genetic risk variants and inflammation play important roles in the development of PD, and there is an overlap between genes associated with increased risk for PD and autoimmune diseases. The pathogenesis of genetic PD is related to inflammatory signaling pathways.