Metallobiology and therapeutic chelation of biometals (copper, zinc and iron) in Alzheimer’s disease: Limitations, and current and future perspectives

Journal of Trace Elements in Medicine and Biology, Journal Year: 2021, Volume and Issue: 67, P. 126779 - 126779

Published: May 15, 2021

Alzheimer's disease (AD) is the most prevalent cause of cognitive impairment and dementia worldwide. The pathobiology has been studied in form several hypotheses, ranging from oxidative stress, amyloid-beta (Aβ) aggregation, accumulation tau forming neurofibrillary tangles (NFT) through metal dysregulation homeostasis, dysfunction cholinergic system, to inflammatory autophagic mechanism. However, none these hypotheses led confirmed diagnostics or approved cure for disease. This review aimed as a basic an encyclopedic short course into metals AD discusses advances chelation strategies developments adopted treatment Since there accumulating evidence role both biometal dyshomeostasis (iron (Fe), copper (Cu), zinc (Zn)) metal-amyloid interactions that lead pathogenesis AD, this focuses on unraveling therapeutic have considered disease, aiming sequester free protein-bound ions reducing cerebral burden. Promising compounds possessing chemically modified moieties evolving multi-target ligands used anti-AD drug candidates are also covered. Several multidirectional multifaceted studies therapeutics show need improved synthesis, screening, analysis be able effectively present chelating drugs. Most limitations their physicochemical properties; some enhance redistribution ions, while others indirectly activate signaling pathways AD. process vivo still needs established design potential bi-functionally well inhibit Aβ aggregation by competing with metal-induced damage neurotoxicity may signal bright end chelation-based

Language: Английский

---

Carbon Dots: A Future Blood–Brain Barrier Penetrating Nanomedicine and Drug Nanocarrier

International Journal of Nanomedicine, Journal Year: 2021, Volume and Issue: Volume 16, P. 5003 - 5016

Published: July 1, 2021

Abstract: Drug delivery across the blood–brain barrier (BBB) is one of biggest challenges in modern medicine due to BBB's highly semipermeable property that limits most therapeutic agents brain diseases enter central nervous system (CNS). In recent years, nanoparticles, especially carbon dots (CDs), exhibit many unprecedented applications for drug delivery. Several types CDs and CD-ligand conjugates have been reported successfully penetrating BBB, which shows a promising progress application CD-based (DDS) treatment CNS diseases. this review, our discussion includes their classification, preparations, structures, properties, neurodegenerative diseases, Alzheimer's disease (AD) tumor. Moreover, abundant functional groups on surface, amine carboxyl groups, allow conjugate with diverse drugs as versatile nanocarriers. addition, structure BBB briefly described, mechanisms transporting various molecules other biological barriers are elucidated. Most importantly, developments BBB-penetrating nanodrugs nanocarriers target tumor summarized. Eventually, future prospects DDS discussed combination development artificial intelligence nanorobots. Keywords: dots, barrier, delivery, tumor,

Language: Английский

---

The Role of Copper Homeostasis in Brain Disease

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(22), P. 13850 - 13850

Published: Nov. 10, 2022

In the human body, copper is an important trace element and a cofactor for several enzymes involved in energy production, iron metabolism, neuropeptide activation, connective tissue synthesis, neurotransmitter synthesis. Copper also necessary cellular processes, such as regulation of intracellular signal transduction, catecholamine balance, myelination neurons, efficient synaptic transmission central nervous system. naturally present some foods available dietary supplement. Only small amounts are typically stored body large amount excreted through bile urine. Given critical role breadth local concentrations distribution transporter proteins brain to maintain steady state internal environment. The dysfunction metabolism or regulatory pathways results imbalance homeostasis brain, which can lead myriad acute chronic pathological effects on neurological function. It suggests unique mechanism linking neuronal activation within This article explores relationship between impaired neuropathophysiological progress diseases.

Language: Английский

---

A review on fluorimetric and colorimetric detection of metal ions by chemodosimetric approach 2013–2021

Coordination Chemistry Reviews, Journal Year: 2022, Volume and Issue: 459, P. 214401 - 214401

Published: Feb. 7, 2022

Language: Английский

---

A review on Rhodamine-based Schiff base derivatives: synthesis and fluorescent chemo-sensors behaviour for detection of Fe³⁺ and Cu²⁺ ions

Journal of Coordination Chemistry, Journal Year: 2023, Volume and Issue: 76(3-4), P. 371 - 402

Published: Feb. 16, 2023

Rhodamine Schiff bases as fluorescent chemo-sensors, fluorogenic cation sensors, is scientifically exigent work. base derivatives have gained attention due to their structural variability. The combination of donor and acceptor groups with delocalized π-orbital results in excellent properties intramolecular charge transfer (ICT) opening spirolactam ring moiety. In this review, we summarize information about sensors reported over the past two decades (2002–2022). We focused on design, synthesis, sensing mechanism (ON/OFF, OFF/ON, ON-OFF-OFF) these for Fe3+ Cu2+ metal ions, well practical applications. also examined how photophysical change when they coordinate resulting changes typical behaviour, such a hypochromic/hyperchromic or hypsochromic/bathochromic shift. anticipate that review will provide fundamental framework researchers further investigate Schiff-based sensors.

Language: Английский

---

Flavonoids and their role in oxidative stress, inflammation, and human diseases

Chemico-Biological Interactions, Journal Year: 2025, Volume and Issue: unknown, P. 111489 - 111489

Published: March 1, 2025

Oxidative stress and chronic inflammation are important drivers in the pathogenesis progression of many diseases, such as cancers breast, kidney, lung, others, autoimmune diseases (rheumatoid arthritis), cardiovascular (hypertension, atherosclerosis, arrhythmia), neurodegenerative (Alzheimer's disease, Parkinson's Huntington's disease), mental disorders (depression, schizophrenia, bipolar disorder), gastrointestinal (inflammatory bowel colorectal cancer), other disorders. With increasing demand for less toxic more tolerable therapies, flavonoids have potential to effectively modulate responsiveness conventional therapy radiotherapy. Flavonoids polyphenolic compounds found fruits, vegetables, grains, plant-derived beverages. Six twelve structurally different flavonoid subgroups dietary significance include anthocyanidins (e.g. pelargonidin, cyanidin), flavan-3-ols epicatechin, epigallocatechin), flavonols quercetin, kaempferol), flavones luteolin, baicalein), flavanones hesperetin, naringenin), isoflavones (daidzein, genistein). The health benefits related their structural characteristics, number position hydroxyl groups presence C2=C3 double bonds, which predetermine ability chelate metal ions, terminate ROS radicals formed by Fenton reaction), interact with biological targets trigger a response. Based on these can exert both antioxidant or prooxidant properties, activity ROS-scavenging enzymes expression activation proinflammatory cytokines (e.g., interleukin-1beta (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α)), induce apoptosis autophagy, target key signaling pathways, nuclear factor erythroid 2-related 2 (Nrf2) Bcl-2 family proteins. This review aims briefly discuss mutually interconnected aspects oxidative inflammatory mechanisms, lipid peroxidation, protein oxidation, DNA damage, mechanism resolution inflammation. major part this article discusses role alleviating inflammation, two common components human diseases. results epidemiological studies also presented.

Language: Английский

---

Oxidative Stress in Alzheimer’s Disease: Are We Connecting the Dots?

Journal of Medicinal Chemistry, Journal Year: 2013, Volume and Issue: 57(7), P. 2821 - 2831

Published: Oct. 16, 2013

Redox impairment is a prominent feature of Alzheimer's disease (AD). It has led to the "oxidative stress hypothesis", which proposes antioxidants as beneficial therapeutic tools in AD treatment. To date, wide variety have been examined neuroprotectants. However, success elusive clinical trials. Several factors contributed this failure, including complexity redox system vivo. Potentially critical aspects include fine-tuned equilibrium between antioxidant defenses and free radical production, lack specific target(s), inherent difficulty delivering where they are needed. Herein, we highlight significant progress field. Future directions research also presented.

Language: Английский

---

Rational Design of a Structural Framework with Potential Use to Develop Chemical Reagents That Target and Modulate Multiple Facets of Alzheimer’s Disease

Journal of the American Chemical Society, Journal Year: 2013, Volume and Issue: 136(1), P. 299 - 310

Published: Dec. 27, 2013

Alzheimer's disease (AD) is characterized by multiple, intertwined pathological features, including amyloid-β (Aβ) aggregation, metal ion dyshomeostasis, and oxidative stress. We report a novel compound (ML) prototype of rationally designed molecule obtained integrating structural elements for Aβ aggregation control, chelation, reactive oxygen species (ROS) regulation, antioxidant activity within single molecule. Chemical, biochemical, mobility mass spectrometric, NMR studies indicate that the ML targets metal-free metal-bound (metal–Aβ) species, suppresses in vitro, diminishes toxicity induced metal-treated living cells. Comparison to its moieties (i.e., 4-(dimethylamino)phenol (DAP) (8-aminoquinolin-2-yl)methanol (1)) reactivity with metal–Aβ suggests synergy incorporating components both chelation interaction. Moreover, water-soluble potentially brain permeable, as well regulates formation presence free radicals. Overall, we demonstrate rational structure-based design strategy can generate small target modulate multiple factors, providing new tool uncover address AD complexity.

Language: Английский

---

Design of PLGA-functionalized quercetin nanoparticles for potential use in Alzheimer’s disease

Colloids and Surfaces B Biointerfaces, Journal Year: 2016, Volume and Issue: 148, P. 116 - 129

Published: Sept. 2, 2016

Language: Английский

---

Metal complexes designed to bind to amyloid-β for the diagnosis and treatment of Alzheimer's disease

Chemical Society Reviews, Journal Year: 2014, Volume and Issue: 43(19), P. 6701 - 6715

Published: Jan. 1, 2014

The use radioactive copper and technetium complexes as amyloid imaging agents, the of luminescent metal non-conventional probes formation potential to be inhibitors toxicity are discussed.

Language: Английский

---