Iron Homeostasis Disorder and Alzheimer’s Disease

Peng, Yi; Chang, Xuejiao; Lang, Minglin

doi:10.3390/ijms222212442

Cited by 93 publications

(63 citation statements)

References 168 publications

(244 reference statements)

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“…Ferritin in the cerebrospinal fluid (CSF) of AD patients has been shown significantly increased, which is negatively correlated with cognitive decline and hippocampal atrophy in AD ( Diouf et al, 2019 ). Additionally, iron can enter mitochondria to form iron sulfur cluster and participate in participate in the process of aerobic respiration ( Peng et al, 2021 ).…”

Section: Iron Metabolism In Healthy and Alzheimer’s Disease Brainmentioning

confidence: 99%

Iron Dyshomeostasis and Ferroptosis: A New Alzheimer’s Disease Hypothesis?

Wang

Shen

et al. 2022

Front. Aging Neurosci.

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Iron plays a crucial role in many physiological processes of the human body, but iron is continuously deposited in the brain as we age. Early studies found iron overload is directly proportional to cognitive decline in Alzheimer’s disease (AD). Amyloid precursor protein (APP) and tau protein, both of which are related to the AD pathogenesis, are associated with brain iron metabolism. A variety of iron metabolism-related proteins have been found to be abnormally expressed in the brains of AD patients and mouse models, resulting in iron deposition and promoting AD progression. Amyloid β (Aβ) and hyperphosphorylated tau, two pathological hallmarks of AD, can also promote iron deposition in the brain, forming a vicious cycle of AD development-iron deposition. Iron deposition and the subsequent ferroptosis has been found to be a potential mechanism underlying neuronal loss in many neurodegenerative diseases. Iron chelators, antioxidants and hepcidin were found useful for treating AD, which represents an important direction for AD treatment research and drug development in the future. The review explored the deep connection between iron dysregulation and AD pathogenesis, discussed the potential of new hypothesis related to iron dyshomeostasis and ferroptosis, and summarized the therapeutics capable of targeting iron, with the expectation to draw more attention of iron dysregulation and corresponding drug development.

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Section: Iron Metabolism In Healthy and Alzheimer’s Disease Brainmentioning

confidence: 99%

Iron Dyshomeostasis and Ferroptosis: A New Alzheimer’s Disease Hypothesis?

Wang

Shen

et al. 2022

Front. Aging Neurosci.

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“…There is a close connection between iron homeostasis and the pathology of AD. It has been reported that the translation of amyloid precursor protein APP is directly regulated by cellular iron levels [ 93 ]. Most of the APP is cleaved by a nonamyloid production pathway.…”

Section: Iron Metabolism and Neurodegenerative Diseasesmentioning

confidence: 99%

“…In contrast, iron deficiency increases the activity of furin, which enhances α-secretase and stimulates the nonamyloid production pathway [ 95 ]. Iron may regulate APP processing through IRPS, interacting with the hypothetical IRE in the 5′- untranslated region of APP mRNA [ 93 ]. The translation of APP may therefore be up-regulated under the condition of iron excess, increasing the amount of APP available to enter the amyloid production pathway, thereby resulting in the aggregation of Aβ peptide [ 93 ].…”

Section: Iron Metabolism and Neurodegenerative Diseasesmentioning

confidence: 99%

Iron Metabolism in Aging and Age-Related Diseases

Tian

Yuan

et al. 2022

IJMS

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Iron is a trace metal element necessary to maintain life and is also involved in a variety of biological processes. Aging refers to the natural life process in which the physiological functions of the various systems, organs, and tissues decline, affected by genetic and environmental factors. Therefore, it is imperative to investigate the relationship between iron metabolism and aging-related diseases, including neurodegenerative diseases. During aging, the accumulation of nonheme iron destroys the stability of the intracellular environment. The destruction of iron homeostasis can induce cell damage by producing hydroxyl free radicals, leading to mitochondrial dysfunction, brain aging, and even organismal aging. In this review, we have briefly summarized the role of the metabolic process of iron in the body, then discussed recent developments of iron metabolism in aging and age-related neurodegenerative diseases, and finally, explored some iron chelators as treatment strategies for those disorders. Understanding the roles of iron metabolism in aging and neurodegenerative diseases will fill the knowledge gap in the field. This review could provide new insights into the research on iron metabolism and age-related neurodegenerative diseases.

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“…Currently, mounting evidence indicates that the accumulation of abnormal proteins such as Aβ and p-Tau is closely associated with the dysfunction of the protein quality control system in the brain [ 21 ]. Particularly in the early stage of AD, the synthesis, degradation and removal of essential biology components in the protein quality control system changes, suggesting that the protein quality control system may be a new and potential target of AD therapy [ 22 ].…”

Section: Introductionmentioning

confidence: 99%

Roles and Mechanisms of the Protein Quality Control System in Alzheimer’s Disease

Liu

Ding

et al. 2021

IJMS

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Alzheimer’s disease (AD) is characterized by the deposition of senile plaques (SPs) and the formation of neurofibrillary tangles (NTFs), as well as neuronal dysfunctions in the brain, but in fact, patients have shown a sustained disease progression for at least 10 to 15 years before these pathologic biomarkers can be detected. Consequently, as the most common chronic neurological disease in the elderly, the challenge of AD treatment is that it is short of effective biomarkers for early diagnosis. The protein quality control system is a collection of cellular pathways that can recognize damaged proteins and thereby modulate their turnover. Abundant evidence indicates that the accumulation of abnormal proteins in AD is closely related to the dysfunction of the protein quality control system. In particular, it is the synthesis, degradation, and removal of essential biological components that have already changed in the early stage of AD, which further encourages us to pay more attention to the protein quality control system. The review mainly focuses on the endoplasmic reticulum system (ERS), autophagy–lysosome system (ALS) and the ubiquitin–proteasome system (UPS), and deeply discusses the relationship between the protein quality control system and the abnormal proteins of AD, which can not only help us to understand how and why the complex regulatory system becomes malfunctional during AD progression, but also provide more novel therapeutic strategies to prevent the development of AD.

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Iron Homeostasis Disorder and Alzheimer’s Disease

Cited by 93 publications

References 168 publications

Iron Dyshomeostasis and Ferroptosis: A New Alzheimer’s Disease Hypothesis?

Iron Dyshomeostasis and Ferroptosis: A New Alzheimer’s Disease Hypothesis?

Iron Metabolism in Aging and Age-Related Diseases

Roles and Mechanisms of the Protein Quality Control System in Alzheimer’s Disease

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