Quinoline–sulfonamides as a multi-targeting neurotherapeutic for cognitive decline:in vitro,in silicostudies and ADME evaluation of monoamine oxidases and cholinesterases inhibitors

RSC Advances, Год журнала: 2024, Номер 14(13), С. 8905 - 8920

Опубликована: Янв. 1, 2024

Alzheimer's disease (AD) is a multifactorial irreversible neurological disorder with multiple enzymes involved.

Язык: Английский

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Biotin Mitigates Alcohol Withdrawal‐Induced Anxiety and Depression by Regulating Serotonin Metabolism, BDNF, Inflammation, and Oxidative Stress in Rats

Neuropsychopharmacology Reports, Год журнала: 2025, Номер 45(1)

Опубликована: Янв. 4, 2025

ABSTRACT Introduction Substance use disorders, particularly alcohol represent a significant public health problem, with adolescents vulnerable to their adverse effects. This study examined the possible anxiolytic and antidepressant effects of biotin, crucial vitamin for brain function, in attenuating behavioral neurobiological changes associated withdrawal adolescent rats. Materials Methods Sixty male Sprague–Dawley rats were exposed 20% ethanol solution 21 days, followed by 21‐day drug‐free period assess long‐term physiological changes. Behavioral assessments included Open Field Test, Elevated Plus Maze, Forced Swimming administered post‐withdrawal evaluate anxiety depression behaviors. Additionally, biochemical analyses performed measure serotonin levels, monoamine oxidase‐A (MAO‐A) activity, BDNF concentrations. Results The results indicate that significantly induced anxiety‐ depression‐like behavior However, treatment at higher doses, effectively attenuated these withdrawal‐related Mechanistically, biotin administration was found regulate oxidase brain‐derived neurotrophic factor, glial fibrillary acidic protein, alleviate oxidative stress markers cortical tissue. Discussion this suggest may have therapeutic potential alleviating negative withdrawal, those related depression. Further research is needed elucidate underlying mechanisms examine clinical supplementation individuals undergoing withdrawal.

Язык: Английский

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[125I]IPC-Lecanemab: Synthesis and Evaluation of Aβ-Plaque-Binding Antibody and Comparison with Small-Molecule [18F]Flotaza and [125I]IBETA in Postmortem Human Alzheimer’s Disease

Neurology International, Год журнала: 2024, Номер 16(2), С. 419 - 431

Опубликована: Апрель 8, 2024

Therapeutic antibodies for reducing Aβ plaque load in Alzheimer’s disease (AD) is currently making rapid progress. The diagnostic imaging of AD has been underway and now used clinical studies. Here, we report our preliminary findings on a therapeutic antibody, Lecanemab, postmortem brain anterior cingulate. [125I]5-iodo-3-pyridinecarboxamido-Lecanemab ([125I]IPC-Lecanemab) was prepared by coupling N-succinimidyl-5-([125I]iodo)-3-pyridinecarboxylate with Lecanemab modest yields. distinct binding [125I]IPC-Lecanemab to Aβ-rich regions human brains higher grey matter (GM) containing plaques compared white (WM) (GM/WM 1.6). Anti-Aβ immunostaining correlated regional the brains. consistent small molecules, [18F]flotaza [125I]IBETA, same subjects. [18F]Flotaza however, exhibited significantly GM/WM ratios (>20) [125I]IPC-Lecanemab. Our results suggest that radiolabeled retains ability bind may therefore be useful as PET radiotracer when labeled [124I]IPC-Lecanemab. directly visualize vivo promising antibody treatment planning dosing could complimentary small-molecule assess outcomes interventions.

Язык: Английский

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[18F]Flotaza for Aβ Plaque Diagnostic Imaging: Evaluation in Postmortem Human Alzheimer’s Disease Brain Hippocampus and PET/CT Imaging in 5xFAD Transgenic Mice

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(14), С. 7890 - 7890

Опубликована: Июль 18, 2024

The diagnostic value of imaging Aβ plaques in Alzheimer's disease (AD) has accelerated the development fluorine-18 labeled radiotracers with a longer half-life for easier translation to clinical use. We have developed [

Язык: Английский

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Biotin's Protective Effects Against Nicotine Withdrawal-Induced Anxiety and Depression: Mechanistic Insights into Serotonin, Inflammation, BDNF, and Oxidative Stress in Male Rats

Addiction Neuroscience, Год журнала: 2025, Номер unknown, С. 100199 - 100199

Опубликована: Янв. 1, 2025

Язык: Английский

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Towards Imaging Tau Hyperphosphorylation: Is DYRK1A a Potential Target for Imaging Hyperphosphorylation of Tau? Molecular Modeling Assessment and Synthesis of [125I]Radioiodinated DYRK1A Inhibitor

Molecules, Год журнала: 2025, Номер 30(5), С. 990 - 990

Опубликована: Фев. 21, 2025

Dual specificity tyrosine-phosphorylation regulated kinase 1A (DYRK1A), a phosphorylation kinase, is localized within the central nervous system and linked to hyperphosphorylation of Tau. Imaging DYRK1A may provide an earlier biomarker for Tauopathies, including Alzheimer’s disease (AD). We have used Chimera-Autodock evaluate potential molecules binding site DYRK1A. Five molecules, 10-bromo-2-iodo-11H-indolo[3,2-c]quinoline-6-carboxylic acid (4E3), 10-iodo-11H-indolo[3,2-c]quinoline-6-carboxylic (KuFal184), harmine, 6-(fluoro-3-(1H-pyrrolo[2,3-c]pyridin-1-yl)isoquinolin-5-amine (MK-6240), 6-iodo-3-(1H-pyrrolo[2,3-c]pyridine-1-yl)isoquinoline (IPPI), were found energies −10.4, −10.1, −9.0, −9.1, −9.4 kcal/mole, respectively. Two 4E3 KuFal184, selective DYRK1A, while harmine also had monoamine oxidase A affinity, MK-6240 IPPI affinity Tau present in brain slices AD subject labeled with [125I]IPPI. KuFal184 no effect on [125I]IPPI, suggesting absence overlap two molecules. MK-6240, known agent was, however, able compete The suggest affinities approximately 80–100 nM, which insufficient serve as imaging agent. higher (6 nM DYRK1A) suggested that [125I]KuFal184 be Electrophilic radioiodination was synthesize modest yields (25%) high radiochemical purity (>95%). Preliminary studies showed some selectivity cortical grey matter regions containing

Язык: Английский

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Ferulago angulata Extract Protects against Beta-amyloid-induced Memory Impairment Through Modulation of Monoaminoxidase Enzymes in the Rat’s Hippocampus

Neurochemical Research, Год журнала: 2025, Номер 50(2)

Опубликована: Март 5, 2025

Язык: Английский

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Reduction in [18F]Nifene Binding, a PET imaging Probe for α4β2* Nicotinic acetylcholinergic receptors in Hippocampus-Subiculum of postmortem human Alzheimer’s disease brain

Brain Research, Год журнала: 2025, Номер unknown, С. 149600 - 149600

Опубликована: Март 1, 2025

Язык: Английский

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[18F]Mefway: Imaging Serotonin 5HT1A Receptors in Human Postmortem Alzheimer’s and Parkinson’s Disease Anterior Cingulate. Potential Applications to Human Positron Emission Tomography Studies

Biomolecules, Год журнала: 2025, Номер 15(4), С. 592 - 592

Опубликована: Апрель 16, 2025

Serotonin 5HT1A receptors may be affected in neurodegeneration, such as Alzheimer’s disease (AD) and Parkinson’s (PD). Using the selective receptor positron emission tomography (PET) imaging agent, [18F]mefway, autoradiographic studies from postmortem human brains of AD, PD, cognitively normal (CN) subjects were carried out. Levels [18F]mefway binding compared with monoamine oxidase A (MAO-A) measured using [18F]FAZIN3 dopamine D2/D3 [18F]fallypride same subjects. Autoradiograms brain sections anterior cingulate corpus callosum CN, AD (n = 6 each group) analyzed. Significant increased was found (+30%) PD (+11%) to CN brains. This increase positively correlated binding, suggesting greater availability when MAO-A levels are higher. Differences three groups not significant. Our results support finding that is elevated cortex negatively MAO-A. upregulation potentially a response lower serotonin due activity this region or other neuroinflammatory changes. Thus, potential target for diagnostic therapeutic approaches PD.

Язык: Английский

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Glutamate’s Effects on the N-Methyl-D-Aspartate (NMDA) Receptor Ion Channel in Alzheimer’s Disease Brain: Challenges for PET Radiotracer Development for Imaging the NMDA Ion Channel

Molecules, Год журнала: 2023, Номер 29(1), С. 20 - 20

Опубликована: Дек. 19, 2023

In an effort to further understand the challenges facing in vivo imaging probe development for N-methyl-D-aspartate (NMDA) receptor ion channel, we have evaluated effect of glutamate on Alzheimer’s disease (AD) brain. Human post-mortem AD brain slices frontal cortex and anterior cingulate were incubated with [3H]MK-801 adjacent sections tested Aβ Tau. The binding was measured absence presence glycine. Increased brains observed at baseline glutamate, indicating a significant increase (>100%) glutamate-induced NMDA channel activity compared cognitively normal brains. glycine lower, suggesting decrease co-agonist Our preliminary findings suggest that targeting as well site may be appropriate diagnosis treatment AD. However, low levels indicate hurdles validation.

Язык: Английский

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