α‐Synuclein forms a complex with transcription factor Elk‐1

α‐Synuclein has been identified as a component of Lewy bodies in Parkinson's disease and diffuse Lewy body disease, and glial cytoplasmic inclusions (GCIs) in multiple system atrophy (MSA). To explore the role of α‐synuclein in the pathogenesis, we searched for molecules interacting with α‐synuclein and discovered that GCIs are stained by anti‐Elk‐1 antibody. To seek the role of Elk‐1 in synucleinopathies, we cotransfected α‐synuclein and Elk‐1 to cultured cells, and found small granular structure complexes where the two molecules colocalized. Moreover, α‐synuclein and Elk‐1 were co‐immunoprecipitated from the cell lysates. For formation of the complex, the presence of both ETS and B‐box domains of Elk‐1 was required. Although there was no evidence of direct binding between α‐synuclein and Elk‐1, we discovered that α‐synuclein and Elk‐1 both bind to ERK‐2, a MAP kinase. The effect of α‐synuclein on the MAP kinase pathway was assessed using the Pathdetect system, which showed prominent attenuation of Elk‐1 phosphorylation with α‐synuclein, and especially A53T mutant. Our results suggest that α‐synuclein reacts with the MAP kinase pathway, which might cause dysfunction of neurons and oligodendrocytes and lead to neurodegeneration in Parkinson's disease and MSA.