Lipid peroxidation and oxidative imbalance: early functional events in Alzheimer's disease.
Alzheimer's disease (AD) is a growing public health problem worldwide. Clinically, AD is a progressive neurodegenerative disorder characterized by a global cognitive decline. Accumulating evidence indicates that reactive oxygen species-mediated reactions, particularly of neuronal lipids, are extensive in those AD brain areas directly involved in the disease processes. Traditional views claim that oxidative-mediated tissue injury in the AD brain is the result of neurodegeneration. In recent years, numerous investigations have pointed to the functional importance of oxidative imbalance as a crucial event in mediating AD pathogenesis. The availability of specific and sensitive markers to monitor in vivo oxidative stress, in combination with studies performed in living patients with clinical diagnosis of AD are helping us to elucidate these issues. The evidence we have accumulated so far clearly indicates that oxidative imbalance and subsequent oxidative stress are early events during the evolution of the disease, and secondary to specific mechanism(s) present in AD but not in other neurodegenerative diseases. These new concepts implicate that this phenomenon may play a more important role in AD pathogenesis than previously anticipated, and that any therapeutic intervention targeting oxidative stress should be initiated at the earliest possible stage of the disease.
Praticò
Domenico
D
Center for Experimental Therapeutics, Department of Pharmacology, University of Pennsylvania, School of Medicine, Philadelphia, PA 19104, USA. domenico@spirit.gcrc.upenn.edu
Sung
Syun
S
D000544:Alzheimer Disease / Q000378:metabolism / Q000503:physiopathology*; D003072:Cognition Disorders / Q000175:diagnosis / Q000503:physiopathology; D005625:Frontal Lobe / Q000503:physiopathology; D006801:Humans; D028421:Isoprostanes / Q000378:metabolism; D015227:Lipid Peroxidation / Q000502:physiology*; D018384:Oxidative Stress / Q000502:physiology*; D013702:Temporal Lobe / Q000503:physiopathology; D013997:Time Factors
D028421:Isoprostanes