Oxidative stress mechanisms and potential therapeutics in Alzheimer disease.
Oxidative damage of biological macromolecules is a hallmark of most neurodegenerative disorders such as Alzheimer, Parkinson and diffuse Lewy body diseases. Another important phenomenon involved in these disorders is the alteration of iron and copper homeostasis. Data from the literature support the involvement of metal homeostasis in mitochondrial dysfunction, protein alterations and nucleic acid damage which are relevant in brain function and consequently, in the development of neurodegenerative disorders. Although alterations in transition metal homeostasis, redox activity, and localization are well documented, it must be determined how alterations of specific copper- and iron-containing metalloenzymes are also involved in Alzheimer disease. The clarification of these phenomena can open a new window for understanding the mechanisms underlying neurodegeneration and, consequently, for the development of new therapeutic strategies such as gene therapy and new pharmaceutical formulations with antioxidant and chelating properties.
Moreira
P I
PI
Department of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA.
Siedlak
S L
SL
Aliev
G
G
Zhu
X
X
Cash
A D
AD
Smith
M A
MA
Perry
G
G
D000544:Alzheimer Disease / Q000209:etiology* / Q000503:physiopathology*; D000818:Animals; D003300:Copper / Q000378:metabolism; D006801:Humans; D007501:Iron / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000502:physiology*
D003300:Copper; D007501:Iron