Iron: the Redox-active center of oxidative stress in Alzheimer disease.
Castellani RJ, Moreira PI, Liu G, Dobson J, Perry G, Smith MA, Zhu X.
Department of Pathology, University of Maryland, Baltimore, MD, USA.
Although iron is essential in maintaining the function of the central nervous system, it is a potent source of reactive oxygen species. Excessive iron accumulation occurs in many neurodegenerative diseases including Alzheimer disease (AD), Parkinson's disease, and Creutzfeldt-Jakob disease, raising the possibility that oxidative stress is intimately involved in the neurodegenerative process. AD in particular is associated with accumulation of numerous markers of oxidative stress; moreover, oxidative stress has been shown to precede hallmark neuropathological lesions early in the disease process, and such lesions, once present, further accumulate iron, among other markers of oxidative stress. In this review, we discuss the role of iron in the progression of AD.
PMID: 17508283 [PubMed - indexed for MEDLINE]
A pesar de que el hierro es esencial en mantener la función del sistema nervioso central, es una fuente potencial de formación de especies reactivas de oxígeno. La acumulación excesiva de hierro ocurre en muchas enfermedades neurodegenerativas incluyendo la Enfermedad de Alzheimer, la enfermedad de Parkinson, y la enfermedad de Creutzfedt Jacob, incrementando la posibilidad de que el estrés oxidativo sea participativo en el proceso de neurodegeneración. El Alzheimer en particular, está asociado con numerosos marcadores de estrés oxidativo. Aun mas, el estrés oxidativo se ha visto que ocurre antes de las lesiones neuropatologicas características, y esas lesiones , una vez presentes , comienzan a acumular hierro, entre otros marcadores de estrés oxidativo.
En este año se ha publicado este paper que explica justamente el rol del hierro en el desarrollo de enfermedades neurodegenerativas.
Increased Iron and Free Radical Generation in Preclinical Alzheimer Disease and Mild Cognitive Impairment
Mark A. Smith,a Xiongwei Zhu,a Massimo Tabaton,b Gang Liu,c Daniel W. McKeel, Jr.,d Mark L. Cohen,a Xinglong Wang,a Sandra L. Siedlak,a Takaaki Hayashi,e Masao Nakamura,f Akihiko Nunomura,g and George Perryah
aDepartment of Pathology, Case Western Reserve University, Cleveland, Ohio, USA
bDepartment of Neuroscience, Ophthalmology, and Genetics, University of Genoa, Genoa, Italy
cDepartment of Radiology, University of Utah, Salt Lake City, Utah, USA
dDepartments of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, USA
eHokkaido Institute of Public Health, Kita 19, Nishi 12, Kita-ku, Sapporo, Japan
fDepartment of Chemistry, Asahikawa Medical College, Asahikawa, Japan
gDepartment of Neuropsychiatry, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Chuo, Yamanashi, Japan
hUTSA Neurosciences Institute and Department of Biology, College of Sciences, University of Texas at San Antonio, San Antonio, Texas, USA
Correspondence to: Mark A. Smith, Ph.D., Department of Pathology, Case Western Reserve University, 2103 Cornell Road, Cleveland, Ohio 44106 USA; Tel: 216-368-3670, Fax: 216-368-8964, Email: firstname.lastname@example.org
The publisher's final edited version of this article is available at J Alzheimers Dis.
It is now established that oxidative stress is one of the earliest, if not the earliest, change that occurs in the pathogenesis of Alzheimer's disease (AD). Consistent with this, mild cognitive impairment (MCI), the clinical precursor of AD, is also characterized by elevations in oxidative stress. Since such stress does not operate in vacuo, in this study we sought to determine whether redox-active iron, a potent source of free radicals, was elevated in MCI and preclinical AD as compared to cognitively-intact age-matched control patients. Increased iron was found at the highest levels both in the cortex and cerebellum from the pre-clinical AD/MCI cases. Interestingly, glial accumulations of redox-active iron in the cerebellum were also evident in preclinical AD patients and tend to increase as patients became progressively cognitively impaired. Our findings suggests that an imbalance in iron homeostasis is a precursor to the neurodegenerative processes leading to AD and that iron imbalance is not necessarily unique to affected regions. In fact, an understanding of iron deposition in other regions of the brain may provide insights into neuroprotective strategies. Iron deposition at the preclinical stage of AD may be useful as a diagnostic tool, using iron imaging methods, as well as a potential therapeutic target, through metal ion chelators.
El link para leer el paper entero es este: