Figure 7
From: Midnolin is a novel regulator of parkin expression and is associated with Parkinson’s Disease
A putative signaling pathway of parkin expression induced by MIDN. Under normal conditions, MIDN is upregulated by both NGF, via ERK1/2 and ERK5, and cAMP signaling. MIDN then promotes neurite outgrowth. Parkin gene expression is promoted by MIDN and ATF4 via the CRE binding site in the parkin core promoter. Parkin then promotes the ubiquitination of misfolded proteins and maintains protein quality. Conversely, when MIDN is down-regulated, ATF4 expression levels also decrease, causing a down-regulation of parkin and a consequent accumulation of misfolded proteins, which can act as a trigger for PD.
