High-resolution analytical imaging and electron holography of magnetite particles in amyloid cores of Alzheimer’s disease

Plascencia-Villa, Germán; Ponce, Arturo; Collingwood, Joanna F.; Arellano-Jiménez, M. Josefina; Zhu, Xiongwei; Rogers, Jack T.; Betancourt, I.; José–Yacamán, Miguel; Perry, George

doi:10.1038/srep24873

Cited by 114 publications

(103 citation statements)

References 63 publications

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“…The excess may be stored as Fe 3+ in other proteins such as neuromelanin in dopaminergic neurons (66), hemosiderin in chronic hemorrhage (67) and hemosiderin in tissue iron overload (68), becoming poorly available for conversion into the labile iron pool. Fe 3+ also accumulates as magnetite in the characteristic amyloid plaque pathology of Alzheimer's disease (69). It is assumed that the stored ferric iron (Fe 3+ ) has the same paramagnetic susceptibility of 5 unpaired electrons, but this remains to be proven.…”

Section: Biometals In Health and Diseasesmentioning

confidence: 99%

Clinical quantitative susceptibility mapping (QSM): Biometal imaging and its emerging roles in patient care

Wang

Spincemaille

Liu

et al. 2017

Magnetic Resonance Imaging

207

199

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Quantitative susceptibility mapping (QSM) has enabled MRI of tissue magnetic susceptibility to advance from simple qualitative detection of hypointense blooming artifacts to precise quantitative measurement of spatial biodistributions. QSM technology may be regarded to be sufficiently developed and validated to warrant wide dissemination for clinical applications of imaging isotropic susceptibility, which is dominated by metals in tissue, including iron and calcium. These biometals are highly regulated as vital participants in normal cellular biochemistry, and their dysregulations are manifested in a variety of pathologic processes. Therefore, QSM can be used to assess important tissue functions and disease. To facilitate QSM clinical translation, this review aims to organize pertinent information for implementing a robust automated QSM technique in routine MRI practice and to summarize available knowledge on diseases for which QSM can be used to improve patient care. In brief, QSM can be generated with postprocessing whenever gradient echo MRI is performed. QSM can be useful for diseases that involve neurodegeneration, inflammation, hemorrhage, abnormal oxygen consumption, substantial alterations in highly paramagnetic cellular iron, bone mineralization, or pathologic calcification; and for all disorders in which MRI diagnosis or surveillance requires contrast agent injection. Clinicians may consider integrating QSM into their routine imaging practices by including gradient echo sequences in all relevant MRI protocols.

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Section: Biometals In Health and Diseasesmentioning

confidence: 99%

Clinical quantitative susceptibility mapping (QSM): Biometal imaging and its emerging roles in patient care

Wang

Spincemaille

Liu

et al. 2017

Magnetic Resonance Imaging

207

199

View full text Add to dashboard Cite

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“…The amount of iron (Bulk et al, 2018) and ferritin (the major ironbinding protein of the cell; Kwiatek-Majkusiak et al, 2015) in brain tissue is associated with the extent of amyloid deposition. As well as being elevated in neuronal tissue, iron is enriched in the amyloid plaque itself (Meadowcroft, Peters, Dewal, Connor, & Yang, 2014), where the iron is observed to be found in a mineralized magnetite species in humans and mice models (Ayton, James, & Bush, 2017;Everett et al, 2018;Plascencia-Villa et al, 2016;Telling et al, 2017). Magnetite is not a normal feature of brain tissue, so it is likely that this iron species was deposited by an abnormal pathological process.…”

Section: Iron Pathology In Admentioning

confidence: 99%

Treating Alzheimer's disease by targeting iron

Nikseresht

Bush

Ayton

2019

British J Pharmacology

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No disease modifying drugs have been approved for Alzheimer's disease despite recent major investments by industry and governments throughout the world. The burden of Alzheimer's disease is becoming increasingly unsustainable, and given the last decade of clinical trial failures, a renewed understanding of the disease mechanism is called for, and trialling of new therapeutic approaches to slow disease progression is warranted. Here, we review the evidence and rational for targeting brain iron in Alzheimer's disease. Although iron elevation in Alzheimer's disease was reported in the 1950s, renewed interest has been stimulated by the advancement of fluid and imaging biomarkers of brain iron that predict disease progression, and the recent discovery of the iron‐dependent cell death pathway termed ferroptosis. We review these emerging clinical and biochemical findings and propose how this pathway may be targeted therapeutically to slow Alzheimer's disease progression. Linked Articles This article is part of a themed section on Therapeutics for Dementia and Alzheimer's Disease: New Directions for Precision Medicine. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.18/issuetoc

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“…Transition metals, including copper, iron, and zinc are believed to play important roles in contributing to various amyloid diseases [85–88]. While there are still debates about the inhibitory or accelerating effects these metals may have on amyloid formation in vitro [87,89,90], it is well known that metal dyshomeostasis is associated with neurodegenerative amyloid diseases [87,91].…”

Section: Natural Product-based Amyloid Inhibitorsmentioning

confidence: 99%

Natural product-based amyloid inhibitors

Velander

Henderson

et al. 2017

Biochemical Pharmacology

165

135

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Many chronic human diseases, including multiple neurodegenerative diseases, are associated with deleterious protein aggregates, also called protein amyloids. One common therapeutic strategy is to develop protein aggregation inhibitors that can slow down, prevent, or remodel toxic amyloids. Natural products are a major class of amyloid inhibitors, and several dozens of natural product-based amyloid inhibitors have been identified and characterized in recent years. These plant- or microorganism-extracted compounds have shown significant therapeutic potential from in vitro studies as well as in vivo animal tests. Despite the technical challenges of intrinsic disordered or partially unfolded amyloid proteins that are less amenable to characterizations by structural biology, a significant amount of research has been performed, yielding biochemical and pharmacological insights into how inhibitors function. This review aims to summarize recent progress in natural product-based amyloid inhibitors and to analyze their mechanisms of inhibition in vitro. Major classes of natural product inhibitors and how they were identified are described. Our analyses comprehensively address the molecular interactions between the inhibitors and relevant amyloidogenic proteins. These interactions are delineated at molecular and atomic levels, which include covalent, non-covalent, and metal-mediated mechanisms. In vivo animal studies and clinical trials have been summarized as an extension. To enhance natural product bioavailability in vivo, emerging work using nanocarriers for delivery has also been described. Finally, issues and challenges as well as future development of such inhibitors are envisioned.

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High-resolution analytical imaging and electron holography of magnetite particles in amyloid cores of Alzheimer’s disease

Cited by 114 publications

References 63 publications

Clinical quantitative susceptibility mapping (QSM): Biometal imaging and its emerging roles in patient care

Clinical quantitative susceptibility mapping (QSM): Biometal imaging and its emerging roles in patient care

Treating Alzheimer's disease by targeting iron

Natural product-based amyloid inhibitors

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