scholarly journals Metal ions, Alzheimer's disease and chelation therapy

2011 ◽  
Vol 61 (1) ◽  
pp. 1-14 ◽  
Author(s):  
Ana Budimir
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Metal Ions ◽  
Metal Ion ◽  
Chelation Therapy ◽  
Neurological Diseases ◽  
Ion Homeostasis ◽  
Ionic Balance ◽  
Metal Ion Homeostasis ◽  
Ion Imbalance

Metal ions, Alzheimer's disease and chelation therapyIn the last few years, various studies have been providing evidence that metal ions are critically involved in the pathogenesis of major neurological diseases (Alzheimer, Parkinson). Metal ion chelators have been suggested as potential therapies for diseases involving metal ion imbalance. Neurodegeneration is an excellent target for exploiting the metal chelator approach to therapeutics. In contrast to the direct chelation approach in metal ion overload disorders, in neurodegeneration the goal seems to be a better and subtle modulation of metal ion homeostasis, aimed at restoring ionic balance. Thus, moderate chelators able to coordinate deleterious metals without disturbing metal homeostasis are needed. To date, several chelating agents have been investigated for their potential to treat neurodegeneration, and a series of 8-hydroxyquinoline analogues showed the greatest potential for the treatment of neurodegenerative diseases.

scholarly journals Mutations in Arabidopsis Yellow Stripe-Like1 and Yellow Stripe-Like3 Reveal Their Roles in Metal Ion Homeostasis and Loading of Metal Ions in Seeds

2006 ◽  
Vol 141 (4) ◽  
pp. 1446-1458 ◽  
Author(s):  
Brian M. Waters ◽  
Heng-Hsuan Chu ◽  
Raymond J. DiDonato ◽  
Louis A. Roberts ◽  
Robynn B. Eisley ◽  
...  
Keyword(s):  
Metal Ions ◽  
Metal Ion ◽  
Ion Homeostasis ◽  
Metal Ion Homeostasis ◽  
Yellow Stripe

scholarly journals Live-Cell Imaging of Physiologically Relevant Metal Ions Using Genetically Encoded FRET-Based Probes

Cells ◽  
2019 ◽  
Vol 8 (5) ◽  
pp. 492 ◽  
Author(s):  
Helmut Bischof ◽  
Sandra Burgstaller ◽  
Markus Waldeck-Weiermair ◽  
Thomas Rauter ◽  
Maximilian Schinagl ◽  
...  
Keyword(s):  
Metal Ions ◽  
Metal Ion ◽  
Alkali Metals ◽  
Fluorescent Protein ◽  
Ion Homeostasis ◽  
Large Cell ◽  
Ion Binding ◽  
Fluorescent Properties ◽  
Metal Ion Homeostasis ◽  
Cellular Metal

Essential biochemical reactions and processes within living organisms are coupled to subcellular fluctuations of metal ions. Disturbances in cellular metal ion homeostasis are frequently associated with pathological alterations, including neurotoxicity causing neurodegeneration, as well as metabolic disorders or cancer. Considering these important aspects of the cellular metal ion homeostasis in health and disease, measurements of subcellular ion signals are of broad scientific interest. The investigation of the cellular ion homeostasis using classical biochemical methods is quite difficult, often even not feasible or requires large cell numbers. Here, we report of genetically encoded fluorescent probes that enable the visualization of metal ion dynamics within individual living cells and their organelles with high temporal and spatial resolution. Generally, these probes consist of specific ion binding domains fused to fluorescent protein(s), altering their fluorescent properties upon ion binding. This review focuses on the functionality and potential of these genetically encoded fluorescent tools which enable monitoring (sub)cellular concentrations of alkali metals such as K+, alkaline earth metals including Mg2+ and Ca2+, and transition metals including Cu+/Cu2+ and Zn2+. Moreover, we discuss possible approaches for the development and application of novel metal ion biosensors for Fe2+/Fe3+, Mn2+ and Na+.

The role of metal ions in the virulence and viability of bacterial pathogens

2019 ◽  
Vol 47 (1) ◽  
pp. 77-87 ◽  
Author(s):  
Stephanie L. Begg
Keyword(s):  
Metal Ions ◽  
Metal Ion ◽  
Molecular Mechanisms ◽  
Bacterial Pathogens ◽  
Ion Homeostasis ◽  
Transition Metal Ions ◽  
Metal Ion Homeostasis ◽  
And Function ◽  
Iron Manganese

AbstractMetal ions fulfil a plethora of essential roles within bacterial pathogens. In addition to acting as necessary cofactors for cellular proteins, making them indispensable for both protein structure and function, they also fulfil roles in signalling and regulation of virulence. Consequently, the maintenance of cellular metal ion homeostasis is crucial for bacterial viability and pathogenicity. It is therefore unsurprising that components of the immune response target and exploit both the essentiality of metal ions and their potential toxicity toward invading bacteria. This review provides a brief overview of the transition metal ions iron, manganese, copper and zinc during infection. These essential metal ions are discussed in the context of host modulation of bioavailability, bacterial acquisition and efflux, metal-regulated virulence factor expression and the molecular mechanisms that contribute to loss of viability and/or virulence during host-imposed metal stress.

scholarly journals Recent Development of Bifunctional Small Molecules to Study Metal-Amyloid-β Species in Alzheimer's Disease

2011 ◽  
Vol 2011 ◽  
pp. 1-9 ◽  
Author(s):  
Joseph J. Braymer ◽  
Alaina S. DeToma ◽  
Jung-Suk Choi ◽  
Kristin S. Ko ◽  
Mi Hee Lim
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Metal Ions ◽  
Metal Ion ◽  
Amyloid Β ◽  
Design Strategies ◽  
Chemical Reagents ◽  
Bifunctional Compounds ◽  
Therapeutic Development ◽  
Target Metal

Alzheimer's disease (AD) is a multifactorial neurodegenerative disease related to the deposition of aggregated amyloid-β (Aβ) peptides in the brain. It has been proposed that metal ion dyshomeostasis and miscompartmentalization contribute to AD progression, especially as metal ions (e.g., Cu(II) and Zn(II)) found in Aβ plaques of the diseased brain can bind to Aβ and be linked to aggregation and neurotoxicity. The role of metal ions in AD pathogenesis, however, is uncertain. To accelerate understanding in this area and contribute to therapeutic development, recent efforts to devise suitable chemical reagents that can target metal ions associated with Aβ have been made using rational structure-based design that combines two functions (metal chelation and Aβ interaction) in the same molecule. This paper presents bifunctional compounds developed by two different design strategies (linkage or incorporation) and discusses progress in their applications as chemical tools and/or potential therapeutics.

scholarly journals Metal Ions-Mediated Oxidative Stress in Alzheimer’s Disease and Chelation Therapy

2021 ◽  
Author(s):  
Dongjin Yeo ◽  
Tae Gyu Choi ◽  
Sung Soo Kim
Keyword(s):  
Oxidative Stress ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Metal Ions ◽  
Chelation Therapy ◽  
Amyloid Β ◽  
Past Research ◽  
Ros Production ◽  
Metal Catalyzed ◽  
Patients Experience

Alzheimer’s disease (AD), ranked as the seventh leading cause of death worldwide, is one of the most incidental neurodegenerative disorders. AD patients experience irreparable damages to the brain, indicated as progressive, insidious, and degenerative. Past research has discovered that the amyloid cascade hypothesis best describes the pathophysiological etiology of AD, designating amyloid-β plaques and neurofibrillary tangles as the ‘hallmarks’ of AD pathology. Furthermore, accumulating evidence show that the oxidative stress state, the imbalance between reactive oxygen species (ROS) production and antioxidation, contributes to AD development. This chapter describes the oxidative stress process in AD. It mainly tackles the correlation of metal-catalyzed ROS production with amyloid-β and how it oxidatively damages both the amyloid-β itself and the surrounding molecules, potentially leading to AD. Additionally, both the role of metal chelation therapy as a treatment for AD and its challenges will be mentioned as well. This chapter specially focuses on how metal ions imbalance induces oxidative stress and how it affects AD pathology.

[P2-080]: IDENTIFICATION OF CEREBRAL METAL ION IMBALANCE IN THE BRAIN OF AGEING OCTODON DEGUS: A NATURAL MODEL FOR ALZHEIMER'S DISEASE

2017 ◽  
Vol 13 (7S_Part_12) ◽  
pp. P636-P637 ◽  
Author(s):  
Nady Braidy ◽  
Anne Poljak ◽  
Chris Marjo ◽  
Helen Rutlidge ◽  
Anne Rich ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Metal Ion ◽  
Octodon Degus ◽  
Ion Imbalance ◽  
The Brain

scholarly journals Golgi Metal Ion Homeostasis in Human Health and Diseases

Cells ◽  
2022 ◽  
Vol 11 (2) ◽  
pp. 289
Author(s):  
Jie Li ◽  
Yanzhuang Wang
Keyword(s):  
Metal Ions ◽  
Membrane Trafficking ◽  
Metal Ion ◽  
Secretory Pathway ◽  
Ion Homeostasis ◽  
Protein Glycosylation ◽  
Proper Function ◽  
Metal Ion Homeostasis ◽  
Trafficking Pathway ◽  
Membrane Organelle

The Golgi apparatus is a membrane organelle located in the center of the protein processing and trafficking pathway. It consists of sub-compartments with distinct biochemical compositions and functions. Main functions of the Golgi, including membrane trafficking, protein glycosylation, and sorting, require a well-maintained stable microenvironment in the sub-compartments of the Golgi, along with metal ion homeostasis. Metal ions, such as Ca2+, Mn2+, Zn2+, and Cu2+, are important cofactors of many Golgi resident glycosylation enzymes. The homeostasis of metal ions in the secretory pathway, which is required for proper function and stress response of the Golgi, is tightly regulated and maintained by transporters. Mutations in the transporters cause human diseases. Here we provide a review specifically focusing on the transporters that maintain Golgi metal ion homeostasis under physiological conditions and their alterations in diseases.

Alzheimer’s Disease Targeted Nano-Based Drug Delivery Systems

2020 ◽  
Vol 21 (7) ◽  
pp. 628-646
Author(s):  
Gülcem Altinoglu ◽  
Terin Adali
Keyword(s):  
Alzheimer’S Disease ◽  
Drug Delivery ◽  
Alzheimer's Disease ◽  
Neurological Diseases ◽  
Sustained Drug Release ◽  
Physiochemical Properties ◽  
Conventional Drug ◽  
Health Care Burden ◽  
The Central Nervous System ◽  
Effective Drugs

Alzheimer’s disease (AD) is the most common neurodegenerative disease, and is part of a massive and growing health care burden that is destroying the cognitive function of more than 50 million individuals worldwide. Today, therapeutic options are limited to approaches with mild symptomatic benefits. The failure in developing effective drugs is attributed to, but not limited to the highly heterogeneous nature of AD with multiple underlying hypotheses and multifactorial pathology. In addition, targeted drug delivery to the central nervous system (CNS), for the diagnosis and therapy of neurological diseases like AD, is restricted by the challenges posed by blood-brain interfaces surrounding the CNS, limiting the bioavailability of therapeutics. Research done over the last decade has focused on developing new strategies to overcome these limitations and successfully deliver drugs to the CNS. Nanoparticles, that are capable of encapsulating drugs with sustained drug release profiles and adjustable physiochemical properties, can cross the protective barriers surrounding the CNS. Thus, nanotechnology offers new hope for AD treatment as a strong alternative to conventional drug delivery mechanisms. In this review, the potential application of nanoparticle based approaches in Alzheimer’s disease and their implications in therapy is discussed.

scholarly journals Zinc limitation in Klebsiella pneumoniae profiled by quantitative proteomics influences transcriptional regulation and cation transporter-associated capsule production

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
A. Sukumaran ◽  
S. Pladwig ◽  
J. Geddes-McAlister
Keyword(s):  
Klebsiella Pneumoniae ◽  
Metal Ion ◽  
Ion Homeostasis ◽  
Cellular Protein ◽  
Pcr Analysis ◽  
Phenotypic Analysis ◽  
Metal Ion Homeostasis ◽  
Capsule Production ◽  
The Impact

Abstract Background Microbial organisms encounter a variety of environmental conditions, including changes to metal ion availability. Metal ions play an important role in many biological processes for growth and survival. As such, microbes alter their cellular protein levels and secretion patterns in adaptation to a changing environment. This study focuses on Klebsiella pneumoniae, an opportunistic bacterium responsible for nosocomial infections. By using K. pneumoniae, we aim to determine how a nutrient-limited environment (e.g., zinc depletion) modulates the cellular proteome and secretome of the bacterium. By testing virulence in vitro, we provide novel insight into bacterial responses to limited environments in the presence of the host. Results Analysis of intra- and extracellular changes identified 2380 proteins from the total cellular proteome (cell pellet) and 246 secreted proteins (supernatant). Specifically, HutC, a repressor of the histidine utilization operon, showed significantly increased abundance under zinc-replete conditions, which coincided with an expected reduction in expression of genes within the hut operon from our validating qRT-PCR analysis. Additionally, we characterized a putative cation transport regulator, ChaB that showed significantly higher abundance under zinc-replete vs. -limited conditions, suggesting a role in metal ion homeostasis. Phenotypic analysis of a chaB deletion strain demonstrated a reduction in capsule production, zinc-dependent growth and ion utilization, and reduced virulence when compared to the wild-type strain. Conclusions This is first study to comprehensively profile the impact of zinc availability on the proteome and secretome of K. pneumoniae and uncover a novel connection between zinc transport and capsule production in the bacterial system.

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