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

Talia Ho; Soha Ahmadi; Kagan Kerman

doi:10.1016/j.freeradbiomed.2022.01.025

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

Free Radic Biol Med. 2022 Mar:181:180-196. doi: 10.1016/j.freeradbiomed.2022.01.025. Epub 2022 Jan 29.

Authors

Talia Ho¹, Soha Ahmadi², Kagan Kerman³

Affiliations

¹ Department of Physical and Environmental Sciences, University of Toronto Scarborough, 1265 Military Trail, Toronto, ON, M1C 1A4, Canada; Department of Molecular Genetics, University of Toronto, 1 King's College Circle, Toronto, ON, M5S 1A8, Canada. Electronic address: talia.ho@mail.utoronto.ca.
² Department of Physical and Environmental Sciences, University of Toronto Scarborough, 1265 Military Trail, Toronto, ON, M1C 1A4, Canada; Department of Chemistry, University of Toronto, 80 St. George Street, Toronto, ON, M5S 3H6, Canada. Electronic address: soha.ahmadi@mail.utoronto.ca.
³ Department of Physical and Environmental Sciences, University of Toronto Scarborough, 1265 Military Trail, Toronto, ON, M1C 1A4, Canada; Department of Chemistry, University of Toronto, 80 St. George Street, Toronto, ON, M5S 3H6, Canada. Electronic address: kagan.kerman@utoronto.ca.

PMID: 35092854
DOI: 10.1016/j.freeradbiomed.2022.01.025

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.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Alzheimer Disease* / pathology
Copper*
Glutathione / metabolism
Humans
Oxidation-Reduction
Oxidative Stress / physiology

Substances

Copper
Glutathione