A new hypothesis for Parkinson’s disease pathogenesis: GTPase-p38 MAPK signaling and autophagy as convergence points of etiology and genomics

The combination of genetics and genomics in Parkinson´s disease has recently begun to unveil molecular mechanisms possibly underlying disease onset and progression. In particular, catabolic processes such as autophagy have been increasingly gaining relevance as post-mortem evidence and experimental models suggested a participation in neurodegeneration and alpha-synuclein Lewy body pathology. In addition, familial Parkinson´s disease linked to LRRK2 and alpha-synuclein provided stronger correlation between etiology and alterations in autophagy. More detailed cellular pathways are proposed and genetic risk factors that associate with idiopathic Parkinson´s disease provide further clues in dissecting contributions of single players. Nevertheless, the fine-tuning of these processes remains elusive, as the initial stages of the pathways are not yet clarified.