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Iron and Alzheimer’s Disease

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Brain-Iron Cross Talk

Part of the book series: Nutritional Neurosciences ((NN))

Abstract

Iron is an essential trace element which mainly involves in the metabolism of neurotransmitters and myelin formation in the nervous system. However, its high redox potential can exacerbate bodily oxidative stress and toxicity under extreme concentrations. Thus, brain iron homeostasis is vital to brain health, as tight iron regulations in the CNS prevents abnormal iron localization and catastrophic oxidative damage to cellular structures and components. As such, it is hypothesized that iron dyshomeostasis is strongly associated with the occurrence of neurodegenerative diseases such as AD. Therefore, it is of utmost importance to fully understand the fundamental mechanisms of brain iron metabolism and regulation to better study the beneficial and/or harmful roles of iron in AD. This book chapter presented the pathology of AD and the mechanism of action of iron in the principal pathways of AD development. It is concluded that iron could initiate and contribute to the pathology of AD, as it is significantly associated with key AD protein filaments of Aβ and τ hyperphosphorylation that leads to the accumulation of senile plaques and NFTs. Besides its ability to create free radicals, ferroptosis has been considered to be a significant factor in the neuronal loss of AD through brain cell necrosis and AD neurotoxicity. The ferroptosis pathway has then become a research hotspot by targeting the iron to invent new interventions to counter the onset of AD and its lethal effects on human health.

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Abbreviations

ACh:

Acetylcholine

AD:

Alzheimer’s disease

APOE:

Apolipoprotein-E

APP:

Amyloid precursor protein

Aβ:

Beta-amyloid protein

BBB:

Blood-brain barrier

BMVEC:

Brain microvascular endothelial cells

Ca2+-ATPase:

Calcium ATPase

CDC:

Centers for Disease Control and Prevention

CDK5:

Cyclin-dependent kinase 5

ChEI:

Cholinesterase inhibitor

CNS:

Central nervous system

CSF:

Cerebrospinal fluid

DASH:

Dietary Approaches to Stop Hypertension

DMT1:

Divalent metal transporter

DNA:

Deoxyribonucleic acid

EBN:

Edible bird’s nest

EOAD:

Early-onset Alzheimer’s disease

ER:

Endoplasmic reticulum

ERK:

Extracellular signal-regulated kinase

FDA:

United States Food and Drug Administration

Fe:

Iron

Fe2+:

Ferrous ion

Fe3+:

Ferric ion

GABA:

Gamma aminobutyric acid

GFAP:

Glial fibrillary acidic protein

GPX4:

Glutathione peroxidase 4

GPX4BIKO:

GPX4 brain inducible knockout

GSK3β:

Glycogen synthase kinase 3

Hb:

Haemoglobin

HCP1:

Haem carrier protein

HDAC:

Histone deacetylase

H-ferritin:

Heavy ferritin subunit

His:

Histidine

HO:

Haem-oxygenase

IDA:

Iron-deficiency anaemia

IF:

Interstitial fluid

IRE:

Iron regulatory element

IREG1/Fpn1:

Ferroportin

IRP:

Iron regulatory protein

LOAD:

Late-onset Alzheimer’s disease

LOOH:

Lipid hydroperoxide

MCI:

Mild cognitive impairment

MedDiet:

Mediterranean diet

MIND:

Mediterranean-DASH Intervention for Neurodegenerative Delay

MRI:

Magnetic resonance imaging

mRNA:

Messenger ribonucleic acid

MUFA:

Mono-unsaturated fatty acid

Na+/K+-ATPase:

Sodium-potassium ATPase pump

NBIA:

Neurodegeneration with brain iron accumulation

NFT:

Neurofibrillary tangles

NIH:

National Institutes of Health

NMDA:

N-Methyl-D-Aspartate

NMDAR:

N-Methyl-D-Aspartate receptor

NTBI:

Non-transferrin-bound iron

PD:

Parkinson’s disease

PET:

Positron emission tomography

pH:

Potential/Power of hydrogen

PP2A:

Protein phosphatase 2

PPA:

Primary progressive aphasia

PSEN:

Presenilin

PUFA:

Poly-unsaturated fatty acid

qPCR:

Real-time/Quantitative polymerase chain reaction

RAF:

Rapidly accelerated fibrosarcoma

RAS:

Rat Sarcoma virus protein

RBC:

Red blood cells

RDA:

Recommended daily allowance

RNA:

Ribonucleic acid

ROS:

Reactive oxygen species

rRNA:

Ribosomal ribonucleic acid

RSL3:

RAS-selective lethal 3

RT:

Reminiscence therapy

RT-PCR :

Reverse transcription polymerase chain reaction

SDH:

Succinate dehydrogenase

SPT :

Simulated presence therapy

TCM:

Traditional Chinese medicine

Tf:

Transferrin

Tf-Fe:

Transferrin-bound iron

TfR:

Transferrin receptor

Tim2:

T-cell immunoglobulin mucin domain protein-2

TREM2 :

Triggering receptor expressed on myeloid cells 2

TSA:

Trichostatin A

US:

United States of America

USD:

United States Dollar

UTR:

Untranslated region

WHO:

World Health Organization

τ:

Tau protein

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Correspondence to Shi-Hui Cheng .

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© 2023 The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd.

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Lo, Y.L., Cheng, SH. (2023). Iron and Alzheimer’s Disease. In: Mohamed, W., Brogazzi, N.L., Kostrzewa, R.M. (eds) Brain-Iron Cross Talk. Nutritional Neurosciences. Springer, Singapore. https://doi.org/10.1007/978-981-19-7327-7_7

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