Structural and binding properties of metal ion chelators relevant to Alzheimer's disease. A theoretical investigation

2011 ◽  
Vol 112 (9) ◽  
pp. 2109-2114 ◽  
Author(s):  
Tiziana Marino ◽  
Matej Pavelka ◽  
Marirosa Toscano ◽  
Nino Russo
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Theoretical Investigation ◽  
Metal Ion ◽  
Binding Properties ◽  
Metal Ion Chelators

Copper binding properties of a tau peptide associated with Alzheimer's disease studied by CD, NMR, and MALDI-TOF MS

Peptides ◽  
2006 ◽  
Vol 27 (4) ◽  
pp. 841-849 ◽  
Author(s):  
Qingfeng Ma ◽  
Yanmei Li ◽  
Jintang Du ◽  
Huadong Liu ◽  
Kenji Kanazawa ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Copper Binding ◽  
Binding Properties ◽  
Maldi Tof Ms ◽  
Maldi Tof ◽  
Tof Ms

Multifunctional compounds for the treatment of Alzheimer’s disease

2021 ◽  
Vol 99 (1) ◽  
pp. 1-9
Author(s):  
Tim Storr
Keyword(s):  
Inorganic Chemistry ◽  
Oxidative Stress ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Metal Binding ◽  
Metal Ion ◽  
Aβ Peptide ◽  
Multifunctional Compounds ◽  
Medicinal Inorganic Chemistry ◽  
And Oxidative Stress

Alzheimer’s disease (AD) is the most common form of dementia, and the prevalence of this currently untreatable disease is expected to rise in step with increased global life expectancy. AD is a multifaceted disorder commonly characterized by extracellular amyloid–beta (Aβ) aggregates, oxidative stress, metal ion dysregulation, and intracellular neurofibrillary tangles. This review will focus on medicinal inorganic chemistry strategies to target AD, with a focus on the Aβ peptide and its relation to metal ion dysregulation and oxidative stress. Multifunctional compounds designed to target multiple disease processes have emerged as promising therapeutic options, and recent reports detailing multifunctional metal-binding compounds, as well as discrete metal complexes, will be discussed.

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 Using machine intelligence to uncover Alzheimer’s disease progression heterogeneity

2020 ◽  
Vol 1 (6) ◽  
Author(s):  
Bessi Qorri ◽  
Mike Tsay ◽  
Abhishek Agrawal ◽  
Rhoda Au ◽  
Joseph Gracie
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Metal Ion ◽  
Drug Repurposing ◽  
Machine Intelligence ◽  
Postmortem Brain ◽  
Class Iii ◽  
Biological Mechanisms ◽  
Data Set ◽  
Treatment Pathways

Aim: Research suggests that Alzheimer’s disease (AD) is heterogeneous with numerous subtypes. Through a proprietary interactive ML system, several underlying biological mechanisms associated with AD pathology were uncovered. This paper is an introduction to emerging analytic efforts that can more precisely elucidate the heterogeneity of AD. Methods: A public AD data set (GSE84422) consisting of transcriptomic data of postmortem brain samples from healthy controls (n = 121) and AD (n = 380) subjects was analyzed. Data were processed by an artificial intelligence platform designed to discover potential drug repurposing candidates, followed by an interactive augmented intelligence program. Results: Using perspective analytics, six perspective classes were identified: Class I is defined by TUBB1, ASB4, and PDE5A; Class II by NRG2 and ZNF3; Class III by IGF1, ASB4, and GTSE1; Class IV is defined by cDNA FLJ39269, ITGA1, and CPM; Class V is defined by PDE5A, PSEN1, and NDUFS8; and Class VI is defined by DCAF17, cDNA FLJ75819, and SLC33A1. It is hypothesized that these classes represent biological mechanisms that may act alone or in any combination to manifest an Alzheimer’s pathology. Conclusions: Using a limited transcriptomic public database, six different classes that drive AD were uncovered, supporting the premise that AD is a heterogeneously complex disorder. The perspective classes highlighted genetic pathways associated with vasculogenesis, cellular signaling and differentiation, metabolic function, mitochondrial function, nitric oxide, and metal ion metabolism. The interplay among these genetic factors reveals a more profound underlying complexity of AD that may be responsible for the confluence of several biological factors. These results are not exhaustive; instead, they demonstrate that even within a relatively small study sample, next-generation machine intelligence can uncover multiple genetically driven subtypes. The models and the underlying hypotheses generated using novel analytic methods may translate into potential treatment pathways.

The Aβ Peptide of Alzheimer's Disease Directly Produces Hydrogen Peroxide through Metal Ion Reduction†

Biochemistry ◽  
1999 ◽  
Vol 38 (24) ◽  
pp. 7609-7616 ◽  
Author(s):  
Xudong Huang ◽  
Craig S. Atwood ◽  
Mariana A. Hartshorn ◽  
Gerd Multhaup ◽  
Lee E. Goldstein ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Hydrogen Peroxide ◽  
Metal Ion ◽  
Aβ Peptide

scholarly journals Copper Modulation as a Therapy for Alzheimer's Disease?

2011 ◽  
Vol 2011 ◽  
pp. 1-5 ◽  
Author(s):  
Yasmina Manso ◽  
Gemma Comes ◽  
Juan Hidalgo ◽  
Ashley I. Bush ◽  
Paul A. Adlard
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Metal Ion ◽  
Amyloid A ◽  
Animal Data ◽  
Clinical Literature ◽  
Behavioural Performance

The role of metals in the pathophysiology of Alzheimer's disease (AD) has gained considerable support in recent years, with both in vitro and in vivo data demonstrating that a mis-metabolism of metal ions, such as copper and zinc, may affect various cellular cascades that ultimately leads to the development and/or potentiation of AD. In this paper, we will provide an overview of the preclinical and clinical literature that specifically relates to attempts to affect the AD cascade by the modulation of brain copper levels. We will also detail our own novel animal data, where we treated APP/PS1 (7-8 months old) mice with either high copper (20 ppm in the drinking water), high cholesterol (2% supplement in the food) or a combination of both and then assessedβ-amyloid (Aβ) burden (soluble and insoluble Aβ), APP levels and behavioural performance in the Morris water maze. These data support an interaction between copper/cholesterol and both Aβand APP and further highlight the potential role of metal ion dyshomeostasis in AD.

Alzheimer’s disease: as it was in the beginning

2017 ◽  
Vol 28 (8) ◽  
Author(s):  
Stanislav Kozlov ◽  
Alexei Afonin ◽  
Igor Evsyukov ◽  
Andrei Bondarenko
Keyword(s):  
Alzheimer’S Disease ◽  
Cell Cycle ◽  
Alzheimer's Disease ◽  
Amyloid Beta ◽  
Metal Ion ◽  
Aberrant Cell ◽  
Molecular Abnormalities ◽  
Model Of Alzheimer’S Disease ◽  
Age Related

AbstractSince Alzheimer’s disease was first described in 1907, many attempts have been made to reveal its main cause. Nowadays, two forms of the disease are known, and while the hereditary form of the disease is clearly caused by mutations in one of several genes, the etiology of the sporadic form remains a mystery. Both forms share similar sets of neuropathological and molecular manifestations, including extracellular deposition of amyloid-beta, intracellular accumulation of hyperphosphorylated tau protein, disturbances in both the structure and functions of mitochondria, oxidative stress, metal ion metabolism disorders, impairment of N-methyl-D-aspartate receptor-related signaling pathways, abnormalities of lipid metabolism, and aberrant cell cycle reentry in some neurons. Such a diversity of symptoms led to proposition of various hypotheses for explaining the development of Alzheimer’s disease, the amyloid hypothesis, which postulates the key role of amyloid-beta in Alzheimer’s disease development, being the most prominent. However, this hypothesis does not fully explain all of the molecular abnormalities and is therefore heavily criticized. In this review, we propose a hypothetical model of Alzheimer’s disease progression, assuming a key role of age-related mitochondrial dysfunction, as was postulated in the mitochondrial cascade hypothesis. Our model explains the connections between all the symptoms of Alzheimer’s disease, with particular attention to autophagy, metal metabolism disorders, and aberrant cell cycle re-entry in neurons. Progression of the Alzheimer’s disease appears to be a complex process involving aging and too many protective mechanisms affecting one another, thereby leading to even greater deleterious effects.

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