Alpha-synuclein mRNA iron-responsive element (SNCA mRNA IRE)

The Alpha-synuclein mRNA iron-responsive element (IRE) is a conserved stem-loop structure located within the 5' untranslated region (UTR) of the SNCA gene transcript (Rogers et al., 2011). This regulatory element functions as a sensor for cellular iron levels, binding to iron regulatory proteins (IRPs) to modulate the translation of alpha-synuclein protein (Friedlich et al., 2007). In conditions of high iron, IRPs dissociate from the IRE, allowing for increased translation, whereas low iron levels promote IRP binding and translational repression. Because the accumulation and aggregation of alpha-synuclein are central to the pathogenesis of Parkinson's disease and other synucleinopathies, this mRNA structure has emerged as a novel therapeutic target. Small molecules like buntanetap (Posiphen) are designed to stabilize the IRE-IRP complex or otherwise interfere with translation at this site to reduce the overall burden of alpha-synuclein (Annovis Bio, 2023). By targeting the production of the protein at the translational level, these therapies aim to slow or halt neurodegeneration.

Other names

SNCA 5'-UTR IREAlpha-synuclein 5'-untranslated region iron-responsive elementSNCA IREAlpha-synuclein mRNA 5'-UTR

Small molecule binding to the 5'-UTR IRE of SNCA mRNA to inhibit translation and reduce alpha-synuclein protein levels.