Glutamate: Molecular Mechanisms and Signaling Pathway in Alzheimer’s Disease, a Potential Therapeutic Target

Molecules, Journal Year: 2024, Volume and Issue: 29(23), P. 5744 - 5744

Published: Dec. 5, 2024

Gamma-glutamate is an important excitatory neurotransmitter in the central nervous system (CNS), which plays role transmitting synapses, plasticity, and other brain activities. Nevertheless, alterations glutamatergic signaling pathway are now accepted as a element Alzheimer's disease (AD) pathophysiology. One of most prevalent types dementia older adults AD, progressive neurodegenerative illness brought on by persistent decline cognitive function. Since AD has been shown to be multifactorial, variety pharmaceutical targets may used treat condition. N-methyl-D-aspartic acid receptor (NMDAR) antagonists acetylcholinesterase inhibitors (AChEIs) two drug classes that Food Drug Administration authorized for treatment AD. The AChEIs approved galantamine, donepezil, rivastigmine. However, memantine only non-competitive NMDAR antagonist This review aims outline involvement glutamate (GLU) at molecular level pathways associated with demonstrate target therapeutic potential its receptor. We will also consider opinion leading authorities working this area, drawback existing strategies, direction further investigation.

Language: Английский

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PAMAM-Calix-Dendrimers: Second Generation Synthesis, Fluorescent Properties and Catecholamines Binding

Pharmaceutics, Journal Year: 2022, Volume and Issue: 14(12), P. 2748 - 2748

Published: Dec. 8, 2022

A convenient method for the synthesis of second generation PAMAM dendrimers based on a p-tert-butylthiacalix[4]arene core in cone, partial cone and 1,3-alternate conformations was developed. Unusual fluorescence obtained PAMAM-calix-dendrimers has been found explained. The binding ability synthesized toward catecholamines (dopamine, L-adrenaline L-noradrenaline) shown by UV-Vis, fluorescence, 1D 2D NMR spectroscopy constants (logKa 3.85–4.74) calculated. As shown, bind internal cavities. All studied hormones were most efficiently bound bearing macrocyclic conformation. size formed supramolecular systems dendrimer/catecholamine established DLS method. decrease hemolytic activity with an increase number dendrimer prospects use as drug delivery agents discussed.

Language: Английский

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A Holographic-Type Model in the Description of Polymer–Drug Delivery Processes

Pharmaceuticals, Journal Year: 2024, Volume and Issue: 17(4), P. 541 - 541

Published: April 22, 2024

A unitary model of drug release dynamics is proposed, assuming that the polymer–drug system can be assimilated into a multifractal mathematical object. Then, we made description implies, via Scale Relativity Theory, functionality continuous and undifferentiable curves (fractal or curves), possibly leading to holographic-like behaviors. At such conjuncture, Schrödinger Madelung scenarios become compatible: in scenario, various modes “mimicked” (via period doubling, damped oscillations, modulated “chaotic” regimes), while scenario involves diffusion laws (Fickian non-Fickian diffusions). In conclusion, propose for describing systems. described by employing Theory monofractal case also one.

Language: Английский

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Repurpose Macelignan as a Potential Drug candidate for Alzheimer’s disease: In-Silico Study

Published: July 12, 2024

Acetylcholinesterase (AChE) is the key enzyme that breaks down and deactivates acetylcholine, thereby regulating concentration of neurotransmitters at synapses. Inhibition AChE considered a potential approach for treating Alzheimer’s disease. The plethora natural products undoubtedly possible source inhibitors. Given adverse side effects currently marketed medications, we sought to investigate 94 compounds linked their remarkable inhibition properties along with IC₅₀ values procured from previous wet lab results. With thorough in silico analysis included molecular docking, dynamics (MD) simulation, mechanics Poisson-Boltzmann Surface Area (MM/PBSA), density functional theory (DFT) study, pharmacokinetic properties, identified most potent compound AChE. Significant hydrogen bonding catalytic triad residues AChE, prominent MM/PBSA binding energy -28.97 KJ/mol, stable nature protein-ligand complex about 100ns MD simulation screened macelignan as best inhibitor. Macelignan, affinity -10.6 kcal/mol, demonstrated greater interaction than reference drug, rivastigmine. In addition, it exhibits significant reactivity in substrate pocket an inhibitory (IC₅₀) 4.16 土 0.070 µM. This outcome further supported by favorable displaying positive result towards Lipinski’s rule Five, negative hepatotoxicity AMES toxicity. study carries perspective suggests therapy disease; research necessary.

Language: Английский

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Nanofiber Power: Reinforcing in-situ Hydrogel for Enhanced Rivastigmine Delivery

Journal of Drug Delivery Science and Technology, Journal Year: 2024, Volume and Issue: 101, P. 106253 - 106253

Published: Oct. 2, 2024

Language: Английский

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