Int. J. Mol. Sci. 2009, 10(3), 1226-1260; doi:10.3390/ijms10031226
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Physiological and Pathological Role of Alpha-synuclein in Parkinson’s Disease Through Iron Mediated Oxidative Stress; The Role of a Putative Iron-responsive Element

1,* email, 1, 2, 3 and 1,* email
Received: 31 December 2008; in revised form: 3 March 2009 / Accepted: 11 March 2009 / Published: 17 March 2009
(This article belongs to the Special Issue Advances in Molecular Neuropathology)
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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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MDPI and ACS Style

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.

AMA Style

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.

Chicago/Turabian Style

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.

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