Do glutathione and copper interact to modify Alzheimer's disease pathogenesis?

Abstract

Alzheimer's disease (AD) is a progressive neurodegenerative disorder first described in 1906 that is currently estimated to impact ∼40 million people worldwide. Extensive research activities have led to a wealth of information on the pathogenesis, hallmarks, and risk factors of AD; however, therapeutic options remain extremely limited. The large number of pathogenic factors that have been reported to potentially contribute to AD include copper dyshomeostasis as well as increased oxidative stress, which is related to alterations to molecular antioxidants like glutathione (GSH). While the individual roles of GSH and copper in AD have been studied by many research groups, their interactions have received relatively little attention, although they appear to interact and affect each other's regulation. Existing knowledge on how GSH-copper interactions may affect AD is sparse and lacks focus. This review first highlights the most relevant individual roles that GSH and copper play in physiology and AD, and then collects and assesses research concerning their interactions, in an effort to provide a more accessible and understandable picture of the role of GSH, copper, and their interactions in AD.

Keywords: Alzheimer's disease; Copper; Copper-glutathione complexes; Glutathione; Oxidative stress; Redox homeostasis.