Iron Pathophysiology in Alzheimer’s Diseases

Wang, Tao; Xu, Shuang‐Feng; Fan, Yingcai; Li, Linbo; Guo, Chuangxin

doi:10.1007/978-981-13-9589-5_5

Cited by 47 publications

(26 citation statements)

References 299 publications

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“…Iron metabolism mainly depends on iron regulatory proteins including ferritin, transferrin and transferrin receptor, hepcidin, ferroportin, and lactoferrin. A previous study had demonstrated that abnormal iron metabolism could generate hydroxyl radicals via the Fenton reaction, which could further trigger oxidative stress reactions, damage cell lipids, protein, and DNA structure and function, lead to cell death, and ultimately influence the process of Aβ misfolding and plaque aggregation (Wang et al, 2019). The aggregation and deposition of Aβ in perivascular space may affect the bulk flow in perivascular space, directly leading to the dysfunction of the glymphatic system (Mestre et al, 2017).…”

Section: Discussionmentioning

confidence: 99%

Dysfunction of the Glymphatic System Might Be Related to Iron Deposition in the Normal Aging Brain

Zhou

Shen

et al. 2020

Front. Aging Neurosci.

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Objective: The study aims to detect the potential relationship between iron deposition and the function of the glymphatic system in the normal aging brain.Methods: We recruited 213 healthy participants. We evaluated the function of the glymphatic system using the index for diffusivity along the perivascular space (ALPS-index), assessed iron deposition on quantitative susceptibility mapping (QSM), and analyzed their relationship.Results: The mean age of participants was 60.1 ± 7.3, and 107 (50.2%) were female. The mean ALPS-index was 1.4 ± 0.2. The QSM values of the caudate nucleus, putamen, globus pallidus, thalamus, red nucleus, substantia nigra, and dentate nucleus were all related to the ALPS-index (all P < 0.001).Conclusions: The main finding of the current study is that the regional brain iron deposition was related to the function of the glymphatic system.Advances in knowledge: We first evaluated the relationship between deposition of brain iron and the dysfunction of the glymphatic system.

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Section: Discussionmentioning

confidence: 99%

Dysfunction of the Glymphatic System Might Be Related to Iron Deposition in the Normal Aging Brain

Zhou

Shen

et al. 2020

Front. Aging Neurosci.

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“…Conversely, there are many indications that iron overload and presence of unbound iron in cellular structure have deleterious consequences on mental health. Indeed, excessive iron deposits become prevalent in the cerebral region upon ageing and even more so in the brains of subjects suffering from Parkinson disease [179] or Alzheimer disease [180] diseases, where they are associated with the neurodegeneration observed in these pathologies.…”

Section: Intake or Status In Vitamin C Iron Magnesium And Zinc And mentioning

confidence: 99%

Vitamins and Minerals for Energy, Fatigue and Cognition: A Narrative Review of the Biochemical and Clinical Evidence

et al. 2020

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Vitamins and minerals are essential to humans as they play essential roles in a variety of basic metabolic pathways that support fundamental cellular functions. In particular, their involvement in energy-yielding metabolism, DNA synthesis, oxygen transport, and neuronal functions makes them critical for brain and muscular function. These, in turn, translate into effects on cognitive and psychological processes, including mental and physical fatigue. This review is focused on B vitamins (B1, B2, B3, B5, B6, B8, B9 and B12), vitamin C, iron, magnesium and zinc, which have recognized roles in these outcomes. It summarizes the biochemical bases and actions of these micronutrients at both the molecular and cellular levels and connects them with cognitive and psychological symptoms, as well as manifestations of fatigue that may occur when status or supplies of these micronutrients are not adequate.

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“…One of these disease categories is neurodegeneration with brain iron accumulation (NBIA) disorders, a group of monogenic inherited disorders characterized by iron deposition in the brain. The second category is composed of a various age-associated neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), Friedreich's ataxia, ALS, and stroke (for recent reviews, see literature 13,81,[108][109][110][111] ). We review these two types of ironassociated CNS diseases separately.…”

Section: Deregulated Iron Homeostasis and Neurodegenerative Disordersmentioning

confidence: 99%

“…[295][296][297] A growing body of evidence has implicated elevated brain iron in AD pathogenesis. 109,[298][299][300][301] Iron levels, and specifically of Fe 3þ , are elevated in the hippocampus and cortex of AD patients. 109,298,302,303 Iron accumulation in the hippocampus can be observed in early stages of the disease and is considered to be a strong predictor of AD-related cognitive decline.…”

Section: Age-associated Neurodegenerative Diseasesmentioning

confidence: 99%

“…109,[298][299][300][301] Iron levels, and specifically of Fe 3þ , are elevated in the hippocampus and cortex of AD patients. 109,298,302,303 Iron accumulation in the hippocampus can be observed in early stages of the disease and is considered to be a strong predictor of AD-related cognitive decline. 302,304,305 Expression of FPN1 is reduced in the hippocampus of AD patients and likely causes or contributes to the accumulation of iron.…”

Section: Age-associated Neurodegenerative Diseasesmentioning

confidence: 99%

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Overdosing on iron: Elevated iron and degenerative brain disorders

D’Mello¹,

Kindy

2020

Exp Biol Med (Maywood)

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All cells in organisms ranging from yeast to humans utilize iron as a cofactor or structural element of proteins that function in diverse and critical cellular functions. However, deregulation of the homeostatic mechanisms regulating iron metabolism resulting in a reduction or excess of iron within the cell or outside of it can have serious effects to the health of cells and the organism. This review provides a brief overview of the molecular and cellular mechanisms regulating iron physiology, including the molecules and processes regulating iron uptake, its storage and utilization, its recycling, and its release from the cell, such that the cellular iron levels are sufficient to meet metabolic demand but below those that cause permanent damage. The major focus of review is on the pathological consequences of dysregulation of these homeostatic mechanisms, focusing on the brain. Current advances on the role of iron accumulation to the pathogenesis of rare neurological disorders caused by genetic mutations as well as to the more prevalent and age-associated neurodegenerative diseases are described. Impact statement Brain degenerative disorders, which include some neurodevelopmental disorders and age-associated diseases, cause debilitating neurological deficits and are generally fatal. A large body of emerging evidence indicates that iron accumulation in neurons within specific regions of the brain plays an important role in the pathogenesis of many of these disorders. Iron homeostasis is a highly complex and incompletely understood process involving a large number of regulatory molecules. Our review provides a description of what is known about how iron is obtained by the body and brain and how defects in the homeostatic processes could contribute to the development of brain diseases, focusing on Alzheimer’s disease and Parkinson’s disease as well as four other disorders belonging to a class of inherited conditions referred to as neurodegeneration based on iron accumulation (NBIA) disorders. A description of potential therapeutic approaches being tested for each of these different disorders is provided.

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Iron Pathophysiology in Alzheimer’s Diseases

Cited by 47 publications

References 299 publications

Dysfunction of the Glymphatic System Might Be Related to Iron Deposition in the Normal Aging Brain

Dysfunction of the Glymphatic System Might Be Related to Iron Deposition in the Normal Aging Brain

Vitamins and Minerals for Energy, Fatigue and Cognition: A Narrative Review of the Biochemical and Clinical Evidence

Overdosing on iron: Elevated iron and degenerative brain disorders

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