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Recent Advances in Targeting Transition Metals (Copper, Iron, and Zinc) in Alzheimer’s Disease

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Abstract

Changes in the transition metal homeostasis in the brain are closely linked with Alzheimer’s disease (AD), including intraneuronal iron accumulation and extracellular copper and zinc pooling in the amyloid plague. The brain copper, zinc, and iron surplus are commonly acknowledged characteristics of AD, despite disagreements among some. This has led to the theory that oxidative stress resulting from abnormal homeostasis of these transition metals may be a causative explanation behind AD. In the nervous system, the interaction of metals with proteins appears to be an essential variable in the development or suppression of neurodegeneration. Chelation treatment may be an option for treating neurodegeneration induced by transition metal ion dyshomeostasis. Some clinicians even recommend using chelating agents as an adjunct therapy for AD. The current review also looks at the therapeutic strategies that have been attempted, primarily with metal-chelating drugs. Metal buildup in the nervous system, as reported in the AD, could be the result of compensatory mechanisms designed to improve metal availability for physiological functions.

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Fig. 1
Fig. 2
Fig. 3

Reproduced from Huang et al. [226] with the kind permission of the Copyright © holder, AAAS, 2023, an open-access article distributed under a Creative Commons Attribution License 4.0 (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium

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Data Availability

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Abbreviations

AD:

Alzheimer’s disease

ABAD:

Aβ binding alcohol dehydrogenase

APP:

Amyloid precursor protein

ATP:

Adenosine triphosphate

BBB:

Blood-brain barrier

CNS:

Central nervous system

COX:

Cytochrome oxidase

Cu:

Copper

ETC:

Electron transport chain

Fe:

Iron

GWAS:

Genome-wide association studies

GSH:

Glutathione

NFTs:

Neurofibrillary tangles

NMDARs:

N-Methyl-d-aspartic acid receptors

ROS:

Reactive oxygen species

SNP:

Single-nucleotide polymorphisms

Zn:

Zinc

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  1. Raghuraj Singh, Archna Panghal and Krishna Jadhav contributed equally.

Authors and Affiliations

  1. Pharmaceutical Nanotechnology Lab, Institutes of Nano Science and Technology (INST), Sector 81. Mohali, Punjab, 140306, India

    Raghuraj Singh

  2. Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, Uttar Pradesh, 201002, India

    Raghuraj Singh, Krishna Jadhav & Rahul Kumar Verma

  3. Department of Pharmacology and Toxicology, Facility for Risk Assessment and Intervention Studies, National Institute of Pharmaceutical Education and Research, S.A.S Nagar, Punjab, India

    Archna Panghal

  4. Faculty of Pharmaceutical Sciences, ICFAI University, Baddi, Distt. Solan, Himachal Pradesh, 174103, India

    Ashima Thakur

  5. Department of Pharmaceutical Sciences Hemwati, Nandan Bahuguna Garhwal University (A Central University), Srinagar, Dist. Garhwal (Uttarakhand), 246174, India

    Charan Singh, Manoj Goyal, Jayant Kumar & Ajay G. Namdeo

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Archna Panghal: writing—original draft. Raghuraj Singh: writing—original draft. Krishna Jadhav: writing—original draft. Ashima Thakur: writing—original draft. Rahul Kumar Verma— review and editing. Charan Singh: writing—review and editing. Manoj Goyal: writing—review and editing. Jayant Kumar: conceptualization and writing—review and editing. Ajay G. Namdeo: review and editing.

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Singh, R., Panghal, A., Jadhav, K. et al. Recent Advances in Targeting Transition Metals (Copper, Iron, and Zinc) in Alzheimer’s Disease. Mol Neurobiol (2024). https://doi.org/10.1007/s12035-024-04256-8

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