Physiological and pathological role of alpha-synuclein in Parkinson's disease through iron mediated oxidative stress; the role of a putative iron-responsive element.
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.
Olivares
David
D
Department of Psychiatry-Neuroscience, Massachusetts General Hospital, Harvard Medical School, Charlestown, 02129, USA. david2177@hotmail.com <david2177@hotmail.com>
Huang
Xudong
X
Branden
Lars
L
Greig
Nigel H
NH
Rogers
Jack T
JT
D000818:Animals; D005290:Ferric Compounds / Q000737:chemistry / Q000633:toxicity*; D006801:Humans; D007980:Levodopa / Q000627:therapeutic use; D016631:Lewy Bodies / Q000378:metabolism; D018696:Neuroprotective Agents / Q000627:therapeutic use; D018384:Oxidative Stress / Q000187:drug effects*; D010300:Parkinson Disease / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology*; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D012313:RNA / Q000378:metabolism; D051844:alpha-Synuclein / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
D005290:Ferric Compounds; D018696:Neuroprotective Agents; D051844:alpha-Synuclein; D007980:Levodopa; D012313:RNA