AUTHOR=Ashraf Azhaar , So Po-Wah 

TITLE=Spotlight on Ferroptosis: Iron-Dependent Cell Death in Alzheimer’s Disease

JOURNAL=Frontiers in Aging Neuroscience

VOLUME=Volume 12 - 2020

YEAR=2020

URL=https://www.frontiersin.org/journals/aging-neuroscience/articles/10.3389/fnagi.2020.00196

DOI=10.3389/fnagi.2020.00196

ISSN=1663-4365

ABSTRACT=Alzheimer disease is an emerging global epidemic that is becoming increasingly unsustainable. Most of the clinical trials have been centered around targeting β-amyloid and have met with limited success. There is a great impetus to identify alternative drug targets. Iron appears to be the common theme prevalent across neurodegenerative diseases. Iron has been shown to promote aggregation and pathogenicity of the characteristic aberrant proteins, β-amyloid, tau, α-synuclein and TDP43, in these diseases. Further support for the involvement of iron in pathogenesis is provided by the recent discovery of a new form of cell death, ferroptosis. Arising from iron-dependent lipid peroxidation, ferroptosis is augmented in conditions of cysteine deficiency and glutathione peroxide-4 inactivation. Here, we review the role of ferroptosis, in light of clinical trials, regarding the rationale of targeting ferroptosis to delay the pathogenesis of Alzheimer’s disease, potentially of relevance to other neurodegenerative diseases.