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

Ashraf, Azhaar; So, Po‐Wah

doi:10.3389/fnagi.2020.00196

Cited by 57 publications

(39 citation statements)

References 99 publications

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“…The identification of ferroptosis in in vivo models of Alzheimer’s disease is difficult since specific markers for ferroptotic cells, such as specific antibodies, are not available. In addition, other metal ions, such as copper, can also regulate ferroptosis and lipid peroxidation [ 172 , 173 ]. Taking all under consideration, we still do not know whether ferroptosis is the cause or consequence of neurodegeneration processes such as Alzheimer’s disease.…”

Section: Ferroptosis In Neurodegenerative Diseasesmentioning

confidence: 99%

Ferroptosis Mechanisms Involved in Neurodegenerative Diseases

Reichert

Freitas

Sampaio-Silva

et al. 2020

IJMS

262

148

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Ferroptosis is a type of cell death that was described less than a decade ago. It is caused by the excess of free intracellular iron that leads to lipid (hydro) peroxidation. Iron is essential as a redox metal in several physiological functions. The brain is one of the organs known to be affected by iron homeostatic balance disruption. Since the 1960s, increased concentration of iron in the central nervous system has been associated with oxidative stress, oxidation of proteins and lipids, and cell death. Here, we review the main mechanisms involved in the process of ferroptosis such as lipid peroxidation, glutathione peroxidase 4 enzyme activity, and iron metabolism. Moreover, the association of ferroptosis with the pathophysiology of some neurodegenerative diseases, namely Alzheimer’s, Parkinson’s, and Huntington’s diseases, has also been addressed.

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Section: Ferroptosis In Neurodegenerative Diseasesmentioning

confidence: 99%

Ferroptosis Mechanisms Involved in Neurodegenerative Diseases

Reichert

Freitas

Sampaio-Silva

et al. 2020

IJMS

262

148

View full text Add to dashboard Cite

show abstract

“…The results ( Figure 1 ) showed a marked difference in iron concentrations in FTD patients with respect to AD, suggesting a possible different role for this metal in these two types of dementia. This result should be confirmed in larger cohorts, however, different levels of biological metals in CSF have been showed in different neurodegenerative diseases (Hozumi et al, 2011 ), in particular AD, Amyotrophic Lateral Sclerosis, and Parkinson disease, so it is plausible that a difference exists also in FTD (Ashraf and So, 2020 ).…”

Section: Discussionmentioning

confidence: 72%

“…The imbalance in iron homeostasis in AD and its interaction with the more consolidated biomarkers Aβ and Tau have been described (Ndayisaba et al, 2019 ; Spotorno et al, 2020 ), supporting the conjecture of new therapeutic strategies based on iron chelators or other iron-toxicity counteracting drugs as a valuable approach for AD treatment (Liu et al, 2018 ; Ashraf and So, 2020 ). Several studies supported the notion that brain iron elevation (Lane et al, 2018 ; Ayton et al, 2019 ) or even the levels of iron-related proteins, e.g., plasma transferrin, are associated with AD and cognitive decline (Hare et al, 2015 ; Guan et al, 2020 ).…”

Section: Introductionmentioning

confidence: 92%

Machine Learning Profiling of Alzheimer's Disease Patients Based on Current Cerebrospinal Fluid Markers and Iron Content in Biofluids

Ficiarà

Boschi

Ansari

et al. 2021

Front. Aging Neurosci.

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Alzheimer's disease (AD) is the most common form of dementia, characterized by a complex etiology that makes therapeutic strategies still not effective. A true understanding of key pathological mechanisms and new biomarkers are needed, to identify alternative disease-modifying therapies counteracting the disease progression. Iron is an essential element for brain metabolism and its imbalance is implicated in neurodegeneration, due to its potential neurotoxic effect. However, the role of iron in different stages of dementia is not clearly established. This study aimed to investigate the potential impact of iron both in cerebrospinal fluid (CSF) and in serum to improve early diagnosis and the related therapeutic possibility. In addition to standard clinical method to detect iron in serum, a precise quantification of total iron in CSF was performed using graphite-furnace atomic absorption spectrometry in patients affected by AD, mild cognitive impairment, frontotemporal dementia, and non-demented neurological controls. The application of machine learning techniques, such as clustering analysis and multiclassification algorithms, showed a new potential stratification of patients exploiting iron-related data. The results support the involvement of iron dysregulation and its potential interaction with biomarkers (Tau protein and Amyloid-beta) in the pathophysiology and progression of dementia.

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“…The decrease in the thiols of peptides and proteins is associated with ferroptosis, which is a new type of non-apoptotic cell death via lipid peroxidation, as described below. Most recent reports have shown a relationship between neurodegeneration disease, which is associated with iron-dependent disease, and lipid peroxidation-induced cell death such as ferroptosis [ 6 ]. Lipid peroxidation products and protein aggregation concomitantly increase in neurodegenerative diseases.…”

Section: Introductionmentioning

confidence: 99%

Cell Death via Lipid Peroxidation and Protein Aggregation Diseases

Iuchi

Takai

Higuchi

2021

Biology

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Lipid peroxidation of cellular membranes is a complicated cellular event, and it is both the cause and result of various diseases, such as ischemia-reperfusion injury, neurodegenerative diseases, and atherosclerosis. Lipid peroxidation causes non-apoptotic cell death, which is associated with cell fate determination: survival or cell death. During the radical chain reaction of lipid peroxidation, various oxidized lipid products accumulate in cells, followed by organelle dysfunction and the induction of non-apoptotic cell death. Highly reactive oxidized products from unsaturated fatty acids are detected under pathological conditions. Pathological protein aggregation is the general cause of these diseases. The cellular response to misfolded proteins is well-known as the unfolded protein response (UPR) and it is partially concomitant with the response to lipid peroxidation. Moreover, the association between protein aggregation and non-apoptotic cell death by lipid peroxidation is attracting attention. The link between lipid peroxidation and protein aggregation is a matter of concern in biomedical fields. Here, we focus on lethal protein aggregation in non-apoptotic cell death via lipid peroxidation. We reviewed the roles of protein aggregation in the initiation and execution of non-apoptotic cell death. We also considered the relationship between protein aggregation and oxidized lipid production. We provide an overview of non-apoptotic cell death with a focus on lipid peroxidation for therapeutic targeting during protein aggregation diseases.

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

Cited by 57 publications

References 99 publications

Ferroptosis Mechanisms Involved in Neurodegenerative Diseases

Ferroptosis Mechanisms Involved in Neurodegenerative Diseases

Machine Learning Profiling of Alzheimer's Disease Patients Based on Current Cerebrospinal Fluid Markers and Iron Content in Biofluids

Cell Death via Lipid Peroxidation and Protein Aggregation Diseases

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