Parkinson's disease (PD) is the second most common progressive neurodegenerative disorder after Alzheimer's disease (AD) and represents a large health burden to society. Genetic and oxidative risk factors have been proposed as possible causes, but their relative contribution remains unclear. Dysfunction of alpha-synuclein (alpha-syn) has been associated with PD due to its increased presence, together with iron, in Lewy bodies. Brain oxidative damage caused by iron may be partly mediated by alpha-syn oligomerization during PD pathology. Also, alpha-syn gene dosage can cause familial PD and inhibition of its gene expression by blocking translation via a newly identified Iron Responsive Element-like RNA sequence in its 5'-untranslated region may provide a new PD drug target.
Keywords: 5-UTR: 5’-untranslated region; 6-OHDA: 6-hydroxydopamine; AD: Alzheimer’s disease; CNS: central nervous system; DA: dopamine; DAT: dopamine transporter; DLB: dementia with Lewy Bodies; ER: endoplasmatic reticulum; GCIs: glial cytoplasmic inclusions; GSH: reduced gluthatione; IRE: iron responsive element; IRPs: interacting binding proteins; LBs: Lewy bodies; LNs: Lewy neurites; MPTP: 1-methyl 4-phenyl 1, 2, 3, 6 tetrapyridine; NAC: non-amyloidogenic component; PD: Parkinson’s disease; PLD2: phospholipase D2; PM: plasmatic membrane; ROS: reactive oxygen species; TH: tyrosine hydroxylase; TfR: transferrin receptor; aa: amino acid(s); nt: nucleotide(s); wt: wild-type; α-syn: alpha-synuclein.