Abstract: 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 (α-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 α-syn oligomerization during PD pathology. Also, α-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: PD: Parkinson's disease; AD: Alzheimer's disease; α-syn: alpha-synuclein; PLD2: phospholipase D2; CNS: central nervous system; ER: endoplasmatic reticulum; PM: plasmatic membrane; LBs: Lewy bodies; LNs: Lewy neurites; GCIs: glial cytoplasmic inclusions; DLB: dementia with Lewy Bodies; DA: dopamine; DAT: dopamine transporter; NAC: non-amyloidogenic component; 5-UTR: 5'-untranslated region; IRE: iron responsive element; IRPs: interacting binding proteins; wt: wild-type; ROS: reactive oxygen species; GSH: reduced gluthatione; 6-OHDA: 6-hydroxydopamine; MPTP: 1-methyl 4-phenyl 1; 2; 3; 6 tetrapyridine; TfR: transferrin receptor; TH: tyrosine hydroxylase; nt: nucleotide(s); aa: amino acid(s)
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Olivares, D.; Huang, X.; Branden, L.; Greig, N.H.; Rogers, J.T. Physiological and Pathological Role of Alpha-synuclein in Parkinson’s Disease Through Iron Mediated Oxidative Stress; The Role of a Putative Iron-responsive Element. Int. J. Mol. Sci. 2009, 10, 1226-1260.
Olivares D, Huang X, Branden L, Greig NH, Rogers JT. Physiological and Pathological Role of Alpha-synuclein in Parkinson’s Disease Through Iron Mediated Oxidative Stress; The Role of a Putative Iron-responsive Element. International Journal of Molecular Sciences. 2009; 10(3):1226-1260.
Olivares, David; Huang, Xudong; Branden, Lars; Greig, Nigel H.; Rogers, Jack T. 2009. "Physiological and Pathological Role of Alpha-synuclein in Parkinson’s Disease Through Iron Mediated Oxidative Stress; The Role of a Putative Iron-responsive Element." Int. J. Mol. Sci. 10, no. 3: 1226-1260.