TY - JOUR
T1 - Oxidative stress and redox-active iron in Alzheimer's disease
AU - Honda, Kazuhiro
AU - Casadesus, Gemma
AU - Petersen, Robert B.
AU - Perry, George
AU - Smith, Mark A.
PY - 2004
Y1 - 2004
N2 - Many lines of evidence indicate that oxidative stress is one of the earliest events in the genesis of Alzheimer's disease (AD). Iron is a transition metal capable of generating hydroxyl radicals, the most potent reactive oxygen species. Consequently, a disruption in the metabolism of iron has been postulated to have a role in the pathogenesis of AD. Indeed, both senile plaques and neorofibrillary tangles, the major pathological landmarks of AD, as well as neurons in the earliest stages of the disease, show elevated iron deposition. However, it is clear that the iron bound to lesion-associated proteins such as amyloid-β and tau plays only a minor, late role in the disease, with the RNA-associated iron found in the neuronal cytoplasm occurring early and being of paramount importance. In this regard, it is probably not surprising that there is significant oxidation of cytoplasmic RNA among the populations of neurons vulnerable to AD. In this review, we consider the role of iron-induced oxidative stress as a key event in AD pathophysiology.
AB - Many lines of evidence indicate that oxidative stress is one of the earliest events in the genesis of Alzheimer's disease (AD). Iron is a transition metal capable of generating hydroxyl radicals, the most potent reactive oxygen species. Consequently, a disruption in the metabolism of iron has been postulated to have a role in the pathogenesis of AD. Indeed, both senile plaques and neorofibrillary tangles, the major pathological landmarks of AD, as well as neurons in the earliest stages of the disease, show elevated iron deposition. However, it is clear that the iron bound to lesion-associated proteins such as amyloid-β and tau plays only a minor, late role in the disease, with the RNA-associated iron found in the neuronal cytoplasm occurring early and being of paramount importance. In this regard, it is probably not surprising that there is significant oxidation of cytoplasmic RNA among the populations of neurons vulnerable to AD. In this review, we consider the role of iron-induced oxidative stress as a key event in AD pathophysiology.
KW - Alzheimer's disease
KW - Amyloid-β
KW - Iron
KW - Mitochondria
KW - RNA
KW - Redox
UR - http://www.scopus.com/inward/record.url?scp=1842608804&partnerID=8YFLogxK
U2 - 10.1196/annals.1306.015
DO - 10.1196/annals.1306.015
M3 - Review article
C2 - 15105265
AN - SCOPUS:1842608804
VL - 1012
SP - 179
EP - 182
JO - Annals of the New York Academy of Sciences
JF - Annals of the New York Academy of Sciences
SN - 0077-8923
ER -