Avanafil mediated dual inhibition of IKKβ and TNFR1 in an experimental paradigm of Alzheimer’s disease:
            <i>in silico</i>
            and
            <i>in vivo</i>
            approach

Gurram, Prasada Chowdari; Satarker, Sairaj; Kumar, Gautam; Begum, Farmiza; Mehta, Chetan Hasmukh; Nayak, Usha Y.; Mudgal, Jayesh; Arora, Devinder; Nampoothiri, Madhavan

doi:10.1080/07391102.2022.2156924

Cited by 3 publications

(1 citation statement)

References 76 publications

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“…Molecular dynamic studies confirmed avanafil’s stability with these targets. In a mouse model of lipopolysaccharide (LPS)-induced neuroinflammation and cognitive decline, avanafil at 6 mg/kg improved cognitive performance, reduced Aβ levels, and lowered inflammatory markers and oxidative parameters [ 19 ].…”

Section: Role Of Nf-κb Pathway Inhibitors In Ad Treatmentmentioning

confidence: 99%

NF-κB Pathway and Its Inhibitors: A Promising Frontier in the Management of Alzheimer’s Disease

Sivamaruthi,

Raghani,

Chorawala

et al. 2023

Biomedicines

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The nuclear factor kappa B (NF-κB) pathway has emerged as a pivotal player in the pathogenesis of various diseases, including neurodegenerative illnesses like Alzheimer’s disease (AD). The involvement of the NF-κB pathway in immune system responses, inflammation, oxidative stress, and neuronal survival highlights its significance in AD progression. We discuss the advantages of NF-κB pathway inhibition, including the potential to mitigate neuroinflammation, modulate amyloid beta (Aβ) production, and promote neuronal survival. However, we also acknowledge the limitations and challenges associated with this approach. Balancing the fine line between dampening inflammation and preserving physiological immune responses is critical to avoid unintended consequences. This review combines current knowledge on the NF-κB pathway’s intricate involvement in AD pathogenesis, emphasizing its potential as a therapeutic target. By evaluating both advantages and limitations, we provide a holistic view of the feasibility and challenges of NF-κB pathway modulation in AD treatment. As the quest for effective AD therapies continues, an in-depth understanding of the NF-κB pathway’s multifaceted roles will guide the development of targeted interventions with the potential to improve AD management.

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Section: Role Of Nf-κb Pathway Inhibitors In Ad Treatmentmentioning

confidence: 99%

NF-κB Pathway and Its Inhibitors: A Promising Frontier in the Management of Alzheimer’s Disease

Sivamaruthi,

Raghani,

Chorawala

et al. 2023

Biomedicines

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Dopamine agonist Rotigotine mitigates lipopolysaccharide-induced neuroinflammation and memory impairment in mice

Gurram,

Satarker,

Nassar

et al. 2024

Metab Brain Dis

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Computer-Aided Drug Design towards New Psychotropic and Neurological Drugs

2023

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Central nervous system (CNS) disorders are a therapeutic area in drug discovery where demand for new treatments greatly exceeds approved treatment options. This is complicated by the high failure rate in late-stage clinical trials, resulting in exorbitant costs associated with bringing new CNS drugs to market. Computer-aided drug design (CADD) techniques minimise the time and cost burdens associated with drug research and development by ensuring an advantageous starting point for pre-clinical and clinical assessments. The key elements of CADD are divided into ligand-based and structure-based methods. Ligand-based methods encompass techniques including pharmacophore modelling and quantitative structure activity relationships (QSARs), which use the relationship between biological activity and chemical structure to ascertain suitable lead molecules. In contrast, structure-based methods use information about the binding site architecture from an established protein structure to select suitable molecules for further investigation. In recent years, deep learning techniques have been applied in drug design and present an exciting addition to CADD workflows. Despite the difficulties associated with CNS drug discovery, advances towards new pharmaceutical treatments continue to be made, and CADD has supported these findings. This review explores various CADD techniques and discusses applications in CNS drug discovery from 2018 to November 2022.

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Avanafil mediated dual inhibition of IKKβ and TNFR1 in an experimental paradigm of Alzheimer’s disease: in silico and in vivo approach

Cited by 3 publications

References 76 publications

NF-κB Pathway and Its Inhibitors: A Promising Frontier in the Management of Alzheimer’s Disease

NF-κB Pathway and Its Inhibitors: A Promising Frontier in the Management of Alzheimer’s Disease

Dopamine agonist Rotigotine mitigates lipopolysaccharide-induced neuroinflammation and memory impairment in mice

Computer-Aided Drug Design towards New Psychotropic and Neurological Drugs

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