Structure–Redox–Relaxivity Relationships for Redox Responsive Manganese-Based Magnetic Resonance Imaging Probes DOI Creative Commons
Eric M. Gale, Shreya Mukherjee, Liu C

et al.

Inorganic Chemistry, Journal Year: 2014, Volume and Issue: 53(19), P. 10748 - 10761

Published: Sept. 16, 2014

A library of 10 Mn-containing complexes capable switching reversibly between the Mn(II) and Mn(III) oxidation states was prepared evaluated for potential usage as MRI reporters tissue redox activity. We synthesized N-(2-hydroxybenzyl)-N,N',N'-ethylenediaminetriacetic acid (HBET) N-(2-hydroxybenzyl-N,N',N'-trans-1,2-cyclohexylenediaminetriacetic (CyHBET) ligands functionalized (-H, -OMe, -NO2) at 5-position aromatic ring. The all 5-H 5-NO2 were isolated, but with 5-OMe unstable. (1)H relaxivity isolable measured pH 7.4 37 °C, 1.4 T. Thermodynamic stability, pH-dependent complex speciation, hydration state, water exchange kinetics complexes, pseudo-first order reduction studied using a combination pH-potentiometry, UV-vis spectroscopy, (17)O NMR measurements. effects ligand structural electronic modifications on Mn(II/III) couple by cyclic voltammetry. are potent relaxation agents compared to corresponding species [Mn(II)(CyHBET)(H2O)](2-) exhibiting 7.5-fold higher (3.3 mM(-1) s(-1)) than oxidized form (0.4 s(-1)). At 7.4, exists mixture fully deprotonated (ML) monoprotonated (HML) stability decreases become more electron-releasing (pMn μM [Mn(II)(CyHBET-R')(H2O)](2-) from 7.6 6.2 R' goes -NO2 respectively). HML speciation increases nature phenolato-O donor increases. presence coligand is maintained upon conversion ML, rate ML faster up 2 orders magnitude (k(ex)(310) H[Mn(II)(CyHBET)(H2O)](-) 1.2 × 10(8) 1.0 10(10) s(-1), can be tuned over range 0.30 V (E(1/2) = 0.27-0.57 V) through 5-substituent component. However, care must taken in tuning electronics avoid Mn(III)-ligand autoredox. Taken together, these results serve establish criteria optimizing versus differentials, potential.

Language: Английский

Amyloidβ-Peptide (1–42)-Induced Oxidative Stress in Alzheimer Disease: Importance in Disease Pathogenesis and Progression DOI
D. Allan Butterfield,

Aaron M. Swomley,

Rukhsana Sultana

et al.

Antioxidants and Redox Signaling, Journal Year: 2012, Volume and Issue: 19(8), P. 823 - 835

Published: Dec. 19, 2012

Alzheimer disease (AD) is an age-related neurodegenerative disease. AD characterized by progressive cognitive impairment. One of the main histopathological hallmarks brain presence senile plaques (SPs) and another elevated oxidative stress. The component SPs amyloid beta-peptide (Aβ) that derived from proteolytic cleavage precursor protein.

Language: Английский

Citations

488
Black Phosphorus Nanosheets as a Neuroprotective Nanomedicine for Neurodegenerative Disorder Therapy DOI
Wansong Chen, Jiang Ouyang, Xinyao Yi

et al.

Advanced Materials, Journal Year: 2017, Volume and Issue: 30(3)

Published: Nov. 30, 2017

Transition-metal dyshomeostasis is recognized as a critical pathogenic factor at the onset and progression of neurodegenerative disorder (ND). Excess transition-metal ions such Cu2+ can catalyze generation cytotoxic reactive oxygen species thereafter induce neuronal cell apoptosis. Exploring new chelating agents, which are not only capable capturing excess redox-active metal, but also cross blood-brain barrier (BBB), highly desired for ND therapy. Herein, it demonstrated that 2D black phosphorus (BP) nanosheets capture efficiently selectively to protect cells from -induced neurotoxicity. Moreover, both in vitro vivo studies show BBB permeability BP significantly improved under near-infrared laser irradiation due their strong photothermal effect, overcomes drawback conventional agents. Furthermore, excellent biocompatibility stability guarantee biosafety future clinical applications. Therefore, these features make have great potential work an efficient neuroprotective nanodrug

Language: Английский

Citations

339
Melatonin and its metabolites vs oxidative stress: From individual actions to collective protection DOI Open Access
Annia Galano, Russel J. Reıter

Journal of Pineal Research, Journal Year: 2018, Volume and Issue: 65(1)

Published: June 11, 2018

Abstract Oxidative stress (OS) represents a threat to the chemical integrity of biomolecules including lipids, proteins, and DNA. The associated molecular damage frequently results in serious health issues, which justifies our concern about this phenomenon. In addition enzymatic defense mechanisms, there are compounds (usually referred as antioxidants) that offer protection against oxidative events. Among them, melatonin its metabolites constitute particularly efficient family. They OS individual entities through wide variety mechanisms electron transfer, hydrogen radical adduct formation, metal chelation, by repairing biological targets. fact, many them can be classified multipurpose antioxidants. However, what seems unique melatonin's family is their collective effects. Because members metabolically related, most expected present living organisms wherever produced. Therefore, exerted may viewed result combined antioxidant effects parent molecule metabolites. Melatonin's rather exceptional regard, offering versatile OS. It certainly one best nature's defenses damage.

Language: Английский

Citations

291
Recent progress in the identification of selective butyrylcholinesterase inhibitors for Alzheimer's disease DOI
Qi Li, Hongyu Yang, Yao Chen

et al.

European Journal of Medicinal Chemistry, Journal Year: 2017, Volume and Issue: 132, P. 294 - 309

Published: March 27, 2017

Language: Английский

Citations

269
Free radicals and polyphenols: The redox chemistry of neurodegenerative diseases DOI
Sonia Losada‐Barreiro, Carlos Bravo‐Díaz

European Journal of Medicinal Chemistry, Journal Year: 2017, Volume and Issue: 133, P. 379 - 402

Published: March 29, 2017

Language: Английский

Citations

259
Computational strategies for predicting free radical scavengers' protection against oxidative stress: Where are we and what might follow? DOI Open Access
Annia Galano, J. Raúl Alvarez‐Idaboy

International Journal of Quantum Chemistry, Journal Year: 2018, Volume and Issue: 119(2)

Published: May 20, 2018

Abstract Oxidative stress, which is frequently induced by an overproduction of free radicals (FR), poses a high risk to human health. Thus, finding efficient strategies for scavenging FR research area current interest. Among many other aspects, this involves identifying chemical compounds capable offering antioxidant protection (AOP) and quantifying such protection. This review summarizes different computational approaches that can contribute gain deeper knowledge on subject. Several reaction mechanisms may AOP are discussed, as well some key factors influencing their relative importance including the nature reacting FR, polarity environment pH in aqueous solution. Kinetics‐based analyses characterize antioxidants, through activity, presented. Trends from data currently available literature provided. Some regarding AOP, still deserves further investigation, discussed.

Language: Английский

Citations

232
Two-dimensional biomaterials: material science, biological effect and biomedical engineering applications DOI
Hui Huang, Wei Feng, Yu Chen

et al.

Chemical Society Reviews, Journal Year: 2021, Volume and Issue: 50(20), P. 11381 - 11485

Published: Jan. 1, 2021

To date, nanotechnology has increasingly been identified as a promising and efficient means to address number of challenges associated with public health. In the past decade, two-dimensional (2D) biomaterials, unique nanoplatform planar topology, have attracted explosive interest in various fields such biomedicine due their morphology, physicochemical properties biological effect. Motivated by progress graphene biomedicine, dozens types ultrathin 2D biomaterials found versatile bio-applications, including biosensing, biomedical imaging, delivery therapeutic agents, cancer theranostics, tissue engineering, well others. The effective utilization stems from in-depth knowledge structure-property-bioactivity-biosafety-application-performance relationships. A comprehensive summary for is still lacking. this review, we aim concentrate on state-of-the-art particular focus applications. particular, discuss design, fabrication functionalization used diverse applications based up-to-date progress. Furthermore, interactions between systems spatial-temporal scale are highlighted, which will deepen understanding underlying action mechanism aiding design improved functionalities. Finally, taking bench-to-bedside focus, conclude review proposing current crucial issues/challenges presenting future development directions advance clinical translation these emerging biomaterials.

Language: Английский

Citations

196
Recent advances in Alzheimer’s disease: Mechanisms, clinical trials and new drug development strategies DOI Creative Commons
Jifa Zhang, Yinglu Zhang, Jiaxing Wang

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: Aug. 23, 2024

Abstract Alzheimer’s disease (AD) stands as the predominant form of dementia, presenting significant and escalating global challenges. Its etiology is intricate diverse, stemming from a combination factors such aging, genetics, environment. Our current understanding AD pathologies involves various hypotheses, cholinergic, amyloid, tau protein, inflammatory, oxidative stress, metal ion, glutamate excitotoxicity, microbiota-gut-brain axis, abnormal autophagy. Nonetheless, unraveling interplay among these pathological aspects pinpointing primary initiators require further elucidation validation. In past decades, most clinical drugs have been discontinued due to limited effectiveness or adverse effects. Presently, available primarily offer symptomatic relief often accompanied by undesirable side However, recent approvals aducanumab ( 1 ) lecanemab 2 Food Drug Administration (FDA) present potential in disrease-modifying Nevertheless, long-term efficacy safety need Consequently, quest for safer more effective persists formidable pressing task. This review discusses pathogenesis, advances diagnostic biomarkers, latest updates trials, emerging technologies drug development. We highlight progress discovery selective inhibitors, dual-target allosteric modulators, covalent proteolysis-targeting chimeras (PROTACs), protein-protein interaction (PPI) modulators. goal provide insights into prospective development application novel drugs.

Language: Английский

Citations

135
Successful therapies for Alzheimer’s disease: why so many in animal models and none in humans? DOI Creative Commons
Rafael Franco, Ángel Cedazo‐Mínguez

Frontiers in Pharmacology, Journal Year: 2014, Volume and Issue: 5

Published: June 25, 2014

Peering into the field of Alzheimer's disease (AD) outsider realizes that many therapeutic strategies tested (in animal models) have been successful. One also may notice there is a deficit in translational research, i.e. to take successful drug mice and translate it patient. Efforts are still focused on novel projects expand arsenal "cure mice". Scientific reasons behind so not obvious. This article aims review current approaches combat AD, open debate common mechanisms cognitive enhancement neuroprotection. In short, either rodent models good should be discontinued, or we extract only most useful information from those models. An example question debated for advancement AD therapy is: addition reducing amyloid tau pathologies, would necessary boost synaptic strength cognition? The provide helpful could turn around negative output generating effective drugs patients. Furthermore, discovery biomarkers human body fluids, clear distinction between enhancers modifying strategies, instrumental advancing anti-AD discovery.

Language: Английский

Citations

160
Neuroprotective Effects of Bioavailable Polyphenol-Derived Metabolites against Oxidative Stress-Induced Cytotoxicity in Human Neuroblastoma SH-SY5Y Cells DOI Creative Commons
Antonio González‐Sarrías, María Ángeles Núñez‐Sánchez, Francisco A. Tómas‐Barberán

et al.

Journal of Agricultural and Food Chemistry, Journal Year: 2016, Volume and Issue: 65(4), P. 752 - 758

Published: Nov. 14, 2016

Oxidative stress is involved in cell death neurodegenerative diseases. Dietary polyphenols can exert health benefits, but their direct effects on neuronal cells are debatable because most phenolics metabolized and do not reach the brain as they occur dietary sources. Herein, we evaluate of a panel bioavailable derived metabolites at physiologically relevant conditions against H2O2-induced apoptosis human neuroblastoma SH-SY5Y cells. Among 19 tested, 3,4-dihydroxyphenylpropionic acid, 3,4-dihydroxyphenylacetic gallic ellagic urolithins prevented via attenuation ROS levels, increased REDOX activity, decreased oxidative stress-induced by preventing caspase-3 activation mitochondrial apoptotic pathway This suggests that sources containing polyphenol precursors these molecules such cocoa, berries, walnuts, tea could be potential functional foods to reduce associated with onset progress

Language: Английский

Citations

151