The 5′-untranslated region of Parkinson's disease α-synuclein messengerRNA contains a predicted iron responsive element

α-Synuclein is the 140 amino acid presynaptic protein^{1, 2} that forms Lewy bodies and other lesions in a spectrum of brain disorders referred to as synucleinopathies, which include Parkinson's disease, the second most common neurodegenerative disorder, as well as dementia with Lewy bodies, Lewy body variant of Alzheimer's disease, multiple system atrophy, and neurodegeneration with brain iron accumulation type I.^{3, 4} A causative role for α-synuclein in neurodegeneration is established by the presence of missense mutations and multiplication of the α-synuclein gene in rare families with autosomal dominant Parkinson's disease.^{3, 4, 5, 6} Thus, factors that regulate production and steady-state levels of α-synuclein are potentially relevant to pathogenesis.

Brain iron homeostasis is known to be disrupted in Parkinson's disease and other synucleinopathies such as neurodegeneration with brain iron accumulation type I,⁷ but the link between iron and α-synuclein pathology has remained unclear. Iron homeostasis is achieved in part by post-transcriptional regulation through highly conserved messenger RNA (mRNA) stem loops called iron regulatory elements (IREs), which are present in the untranslated regions (UTRs) of a number of transcripts essential to iron metabolism.^{7, 8} Here we provide the first report of a putative IRE in the 5′-UTR of mRNA encoding the 140-residue α-synuclein and predict that this RNA structure post-transcriptionally regulates α-synuclein protein production in response to cellular iron and redox events.