Xiongwei Zhu

Antioxidant approaches for the treatment of Alzheimer's disease.

Oxidative stress is an important factor, and one that acts in the earliest stages, of Alzheimer’s disease (AD) pathogenesis. The reduction of oxidative stress has been tested as a therapy for AD. While the trial of vitamin E supplementation in moderately severe AD is the most promising so far, it also reveals the limitations of general antioxidant therapies that simply lower oxidative stress and, therefore, the complexity of the redox system. The multiple contributing factors that foster the clinical manifestations of AD should be considered when designing antioxidative stress therapy. In this article, we discuss the multiple pathogenic mechanisms of oxidative stress in AD and the potential targeting approaches.

Antioxidant Therapy in Alzheimer’s Disease: Theory and Practice

Alzheimer disease treatment has yet to yield a successful therapy that addresses the source of the damage found in brains. Of the varied proposed theories of AD etiology, reactive oxygen species (ROS) generation is cited as a common factor. Efforts to reduce the pathology associated with ROS via antioxidants therefore offer new hope to patients suffering from this devastative disease.

Hypoxia tolerance in mammalian heterotherms

SUMMARY Heterothermic mammals tolerate severe hypoxia, as well as a variety of central nervous system insults, better than homeothermic mammals. Tolerance to hypoxia may stem from adaptations associated with the ability to survive hibernation and periodic arousal thermogenesis. Here, we review evidence and mechanisms of hypoxia tolerance during hibernation, euthermy and arousal in heterothermic mammals and consider potential mechanisms for regenerative-like processes, such as synaptogenesis, observed within hours of hypoxic stress associated with arousal thermogenesis.

Neurofibrillary Tangle Formation as a Protective Response to Oxidative Stress in Alzheimer’s Disease

Neurofibrillary tangles (NFTs) composed of hyperphosphorylated tau are major hallmarks of Alzheimer’s disease (AD). Because the formation of NFTs reflects a hierarchy of neuronal vulnerability and their distribution parallels disease severity, NFTs formation has been suspected to play a major role in the disease pathogenesis. However, theoretically, either pathogenic alterations of the disease or protective responses to the disease pathogenesis can be observed according to the hierarchy of the vulnerability. Indeed, the majority of neuronal death in AD likely occurs without the process of NFT formation and neurons may live for decades with NFTs. More important, there is a growing body of evidence suggesting that tau phosphorylation and conformational changes are inducible by oxidative insults and the neuronal oxidative damage in AD is actually alleviated through the process of NFT formation. In line with recent evidence that neuronal cellular inclusions represent a protective function, rather than being initiators or accelerators of disease pathogenesis, we suspect that the NFTs function as a cytoprotective response especially a primary line of antioxidant defense. An involvement of tau phosphorylation in the insulin-like signaling pathway affecting organism longevity implicates an essential link between NFT formation and an adaptation under oxidative stress in age-associated neurodegeneration.