Year-end Sale % OFF 
Abstract
Alzheimer’s 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 peroxidase-4 inactivation. Here, we review clinical trials that provide the rationale for targeting ferroptosis to delay the pathogenesis of Alzheimer’s disease (AD), potentially of relevance to other neurodegenerative diseases.
Highlights
Alzheimer’s disease (AD) is increasing at an alarming rate and is an emerging epidemic
Combining the different lines of evidence, a pivotal involvement of proteinopathies is indicated in inducing iron dyshomeostasis, lipid peroxidation, and mitochondrial damage which are reminiscent of changes consistent with ferroptosis
mild cognitive impairment (MCI) and AD subjects supplemented with combined N-acetylcysteine, α-tocopherol, folate, vitamin B12, methionine, acetyl-L-carnitine demonstrated either stable or improved cognitive performance and mood/behavior (Remington et al, 2015a,b, 2016)
Summary
Alzheimer’s disease (AD) is increasing at an alarming rate and is an emerging epidemic. Combining the different lines of evidence, a pivotal involvement of proteinopathies is indicated in inducing iron dyshomeostasis, lipid peroxidation, and mitochondrial damage which are reminiscent of changes consistent with ferroptosis This proposition awaits experimental validation to elucidate a direct role of the misfolded proteins in ferroptosis in the context of neurodegenerative diseases. Deferiprone is an orally active, brain penetrant iron-chelator, approved for use in β-thalassemia, currently, undergoing a Phase II clinical trial in mild cognitive impairment (MCI) and AD (Deferiprone to Delay Dementia—clinicaltrials.gov identifier: NCT03235686; Nikseresht et al, 2019). Since iron is an essential cofactor in multi-fold cellular processes, iron-chelation can have off-target effects and potentially cause untoward effects
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
