Recent progress in the development of fluorescent probes for imaging pathological oxidative stress

Chemical Society Reviews, Journal Year: 2023, Volume and Issue: 52(11), P. 3873 - 3926

Published: Jan. 1, 2023

Oxidative stress is closely related to the physiopathology of numerous diseases. Reactive oxygen species (ROS), reactive nitrogen (RNS), and sulfur (RSS) are direct participants important biomarkers oxidative stress.

Language: Английский

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Chemical Design of Activatable Photoacoustic Probes for Precise Biomedical Applications

Chemical Reviews, Journal Year: 2022, Volume and Issue: 122(6), P. 6850 - 6918

Published: March 2, 2022

Photoacoustic (PA) imaging technology, a three-dimensional hybrid modality that integrates the advantage of optical and acoustic imaging, has great application prospects in molecular due to its high depth resolution. To endow PA with ability for real-time visualization precise biomedical diagnosis, numerous activatable probes which can specifically alter their intensities upon reacting targets or biological events interest have been developed. This review highlights recent developments applications including detection biotargets events. First, generation mechanism signals will be given, followed by brief introduction contrast agents used probe design. Then we particularly summarize general design principles alteration strategies developing probes. Furthermore, give detailed discussion living systems. At last, current challenges outlooks future discussed. We hope this stimulate new ideas explore potentials future.

Language: Английский

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Simulation Studies of Amyloidogenic Polypeptides and Their Aggregates

Chemical Reviews, Journal Year: 2019, Volume and Issue: 119(12), P. 6956 - 6993

Published: April 11, 2019

Amyloids, fibrillar assembly of (poly)peptide chains, are associated with neurodegenerative illnesses such as Alzheimer's and Parkinson's diseases, for which there no cures. The molecular mechanisms the formation toxic species still elusive. Some peptides proteins can form functional amyloid-like aggregates mainly in bacteria fungi but also humans. Little is known on differences self-assembly pathogenic (poly)peptides. We review atomistic coarse-grained simulation studies amyloid their monomeric, oligomeric, states. Particular emphasis given to challenges one faces characterize at atomic level detail conformational space disordered (poly)peptides aggregation. discuss difficulties comparing results experimental data, we propose new shed light aggregation processes diseases.

Language: Английский

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Alzheimer’s disease: Insights and new prospects in disease pathophysiology, biomarkers and disease-modifying drugs

Biochemical Pharmacology, Journal Year: 2023, Volume and Issue: 211, P. 115522 - 115522

Published: March 28, 2023

Alzheimer's disease (AD) is one of the most prevalent neurodegenerative diseases that affect millions people worldwide, with both prevalence and incidence increasing age. It characterized by cognitive decline associated, specifically, degeneration cholinergic neurons. The problem this even more fundamental as available therapies remain fairly limited mainly focused on symptoms' relief. Although aetiology remains elusive, two main pathological hallmarks are described: i) presence neurofibrillary tangles formed unfolded protein aggregates (hyperphosphorylated Tau protein) ii) extracellular amyloid-beta peptide. Given complexity surrounding pathogenesis disease, several potential targets have been highlighted interrelated upon its progression, such oxidative stress accumulation metal ions. Thus, advances made development innovative multitarget therapeutical compounds to delay progression restore cell function. This review focuses ongoing research new insights emerging disease-modifying drugs for AD treatment. Furthermore, classical novel biomarkers early diagnosis their role in assisting improvement targeted will also be approached.

Language: Английский

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Synthetic α-glucosidase inhibitors as promising anti-diabetic agents: Recent developments and future challenges

European Journal of Medicinal Chemistry, Journal Year: 2023, Volume and Issue: 249, P. 115119 - 115119

Published: Jan. 17, 2023

Language: Английский

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Direct Quantification and Visualization of Homocysteine, Cysteine, and Glutathione in Alzheimer’s and Parkinson’s Disease Model Tissues

Analytical Chemistry, Journal Year: 2021, Volume and Issue: 93(28), P. 9878 - 9886

Published: July 7, 2021

Alzheimer's disease (AD) and Parkinson's (PD) are chronic neurodegenerative diseases with high morbidity mortality. Homocysteine (Hcy), cysteine (Cys), glutathione (GSH) closely related to AD PD. However, the dynamics of Hcy, Cys, GSH in brain tissues potential pathogenesis between Cys/Hcy/GSH PD remain unclear. Herein, a novel fluorescent probe 1 multiple binding sites was rationally designed exploited for direct quantification serum total Hcy Cys along superior optical properties. Importantly, differentiation simultaneity fluorescence imaging were achieved living cells, tissues, mouse models this probe, providing evidences relationship Hcy/Cys/GSH AD/PD first time. In addition, studies demonstrated that elevated levels imbalanced redox homeostasis, increased amyloid aggregates, nerve cell cytotoxicity. These findings will greatly promote understanding functions diseases, demonstrating clinical promise early diagnosis prevention

Language: Английский

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Current Strategies for Modulating Aβ Aggregation with Multifunctional Agents

Accounts of Chemical Research, Journal Year: 2021, Volume and Issue: 54(9), P. 2172 - 2184

Published: April 21, 2021

Alzheimer's disease (AD), as the primary cause of dementia, has seriously affected millions people worldwide and brought a very heavy financial social burden. With growth population aging, situation will worsen unless efficacious drugs are found to reverse, stop, or even slow down progression. More more evidence demonstrated that amyloid-β (Aβ) aggregation is an upstream causative factor in AD pathogenesis then triggers slew pathological events. Furthermore, concentrated redox metal ions brain, especially Cu(II), can significantly exacerbate Aβ contribute formation neurotoxic reactive oxygen species (ROS). Therefore, inhibition relief amyloidosis-initiated neurotoxicity play critical role treatment. Until now, several methods have been proposed modulate aggregation, such developing inhibitors interfere with assembly via noncovalent interactions, copper chelators cut off metal-accelerated concomitant cytotoxicity, photooxidation reduce hydrophobicity tendency Aβ, thermal dissociation disrupt amyloid aggregates susceptible temperature, degradation artificial protease fracture peptide into small fragments, clearance peripheral bypass obstruction BBB burden.In this Account, we focus on our contributions development Aβ-targeted multifunctional molecules nanoparticles, emphasizing diversified strategies synergistic therapeutic effects. These agents possess following multifunctionalities: (1) compared frequently used restricted by intrinsically feeble sensitive efficiently block exploiting two Aβ-specific simultaneously; (2) apart from regulating multipronged also target other factors pathogenesis, increased oxidative stress, abnormal accumulation, irreversible neuron loss; (3) platforms both diagnostic modalities through integrating situ imaging, real-time diagnostics, multitarget direction, stimuli-responsive drug release, blood-brain barrier (BBB) translocation features instrumental improving levels at trouble sites, diminishing off-target adverse reactions, evaluating effects, averting overtreatment.Given fact local inflammation, dyshomeostasis universal biomarkers shared various neurodegenerative disorders, Account provides perspective for evolution customized multiple reactivities diseases. In addition, recent studies indicated enter nucleus induce DNA damage anomalous conformational transition. We explore influences biological effects aggregates.

Language: Английский

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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

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Imidazole: Synthesis, Functionalization and Physicochemical Properties of a Privileged Structure in Medicinal Chemistry

Molecules, Journal Year: 2023, Volume and Issue: 28(2), P. 838 - 838

Published: Jan. 13, 2023

Imidazole was first synthesized by Heinrich Debus in 1858 and obtained the reaction of glyoxal formaldehyde ammonia, initially called glyoxaline. The current literature provides much information about synthesis, functionalization, physicochemical characteristics biological role imidazole. is a structure that, despite being small, has unique chemical complexity. It nucleus that very practical versatile its construction/functionalization can be considered rich source diversity. acts extremely important processes for maintenance living organisms, such as catalysis enzymatic processes. Imidazole-based compounds with antibacterial, anti-inflammatory, antidiabetic, antiparasitic, antituberculosis, antifungal, antioxidant, antitumor, antimalarial, anticancer, antidepressant many others make up therapeutic arsenal new bioactive proposed most diverse works. interest importance imidazole-containing analogs field medicinal chemistry remarkable, understanding from development blockbuster drug cimetidine explores all concepts imidazole context research drugs.

Language: Английский

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Mitochondrial dysfunctions, oxidative stress and neuroinflammation as therapeutic targets for neurodegenerative diseases: An update on current advances and impediments

Neuroscience & Biobehavioral Reviews, Journal Year: 2022, Volume and Issue: 144, P. 104961 - 104961

Published: Nov. 14, 2022

Language: Английский

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