Understanding of Alzheimer's Disease Pathophysiology for Therapeutic Implications of Natural Products as Neuroprotective Agents

Ageing Research Reviews, Journal Year: 2025, Volume and Issue: unknown, P. 102680 - 102680

Published: Feb. 1, 2025

Language: Английский

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Recent advancement in understanding of Alzheimer's disease: Risk factors, subtypes, and drug targets and potential therapeutics

Ageing Research Reviews, Journal Year: 2024, Volume and Issue: 101, P. 102476 - 102476

Published: Aug. 31, 2024

Language: Английский

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Navigating the Maze of Alzheimer’s disease by exploring BACE1: Discovery, current scenario, and future prospects

Ageing Research Reviews, Journal Year: 2024, Volume and Issue: 98, P. 102342 - 102342

Published: May 16, 2024

Language: Английский

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Newer Therapeutic Approaches in Treating Alzheimer’s Disease: A Comprehensive Review

ACS Omega, Journal Year: 2025, Volume and Issue: 10(6), P. 5148 - 5171

Published: Feb. 3, 2025

Alzheimer's disease (AD) is an aging-related irreversible neurodegenerative affecting mostly the elderly population. The main pathological features of AD are extracellular Aβ plaques generated by APP cleavage through amyloidogenic pathway, intracellular neurofibrillary tangles (NFT) resulting from hyperphosphorylated tau proteins, and cholinergic neurodegeneration. However, actual causes unknown, but several studies suggest hereditary mutations in PSEN1 -2, APOE4, APP, TAU genes major perpetrators. In order to understand etiology pathogenesis AD, various hypotheses proposed. These include following hypotheses: amyloid accumulation, tauopathy, inflammation, oxidative stress, mitochondrial dysfunction, glutamate/excitotoxicity, deficiency, gut dysbiosis. Currently approved therapeutic interventions donepezil, galantamine, rivastigmine, which cholinesterase inhibitors (ChEIs), memantine, N-methyl-d-aspartate (NMDA) antagonist. treatment strategies focus on only symptomatic management attenuating symptoms not regeneration neurons or clearance Tau. This review focuses pathophysiology, novel targets, disease-altering treatments such as α-secretase modulators, active immunotherapy, passive natural antioxidant products, nanomaterials, antiamyloid therapy, aggregation inhibitors, transplantation fecal microbiota stem cells, microtubule stabilizers that clinical trials still under investigation.

Language: Английский

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Temperature-Dependent Aggregation of Tau Protein Is Attenuated by Native PLGA Nanoparticles Under in vitro Conditions

International Journal of Nanomedicine, Journal Year: 2025, Volume and Issue: Volume 20, P. 1999 - 2019

Published: Feb. 1, 2025

Hyperphosphorylation and aggregation of the microtubule-associated tau protein, which plays a critical role in many neurodegenerative diseases (ie, tauopathies) including Alzheimer's disease (AD), are known to be regulated by variety environmental factors temperature. In this study we evaluated effects FDA-approved poly (D,L-lactide-co-glycolic) acid (PLGA) nanoparticles, can inhibit amyloid-β aggregation/toxicity cellular/animal models AD, on temperature-dependent 0N4R isoforms vitro. We have used biophysical (Thioflavin T kinetics, dynamic light scattering asymmetric-flow field-flow fractionation), structural (fluorescence imaging transmission electron microscopy) biochemical (Filter-trap assay detection soluble protein) approaches, evaluate native PLGA nanoparticles aggregation. Our results show that propensity increases significantly dose-dependent manner with rise temperature from 27°C 40°C, as measured lag time rate. Additionally, 2N4R manner. Native inhibits at all temperatures concentration-dependent manner, possibly interacting aggregation-prone hydrophobic hexapeptide motifs tau. is able trigger disassembly preformed aggregates function 40°C. These results, taken together, suggest not only attenuate but also promote aggregates, increased Given evidence influence pathology, believe may unique potential regulate abnormalities associated AD-related pathology.

Language: Английский

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Cardioprotective effects of liposomal resveratrol in diabetic rats: unveiling antioxidant and anti-inflammatory benefits

Redox Report, Journal Year: 2024, Volume and Issue: 29(1)

Published: Nov. 4, 2024

As a consequence of chronic hyperglycemia, diabetes complications and tissue damage are exacerbated. There is evidence that natural phytochemicals, including resveratrol, bioactive polyphenol, may be able to reduce oxidative stress improve insulin sensitivity. However, resveratrol's limited bioavailability hampers its therapeutic effectiveness. By using liposomes, resveratrol better delivered into the body more bioavailable. The objective this study was assess cardioprotective potential liposome-encapsulated (LR) in streptozotocin-induced (STZ) diabetic rat model. Adult male Wistar rats were categorized five groups: control, diabetic, resveratrol-treated (40 mg/kg), liposomal (LR)-treated (20 mg/kg) for five-week period. We compared effects LR those on various parameters, serum levels cardiac markers, pro-inflammatory cytokines, nuclear transcription factor, apoptotic markers. treatment STZ-diabetic resulted notable physiological improvements, blood glucose regulation, inflammation reduction, mitigation, apoptosis inhibition. effectively lowered enhanced cardiovascular function. It also demonstrated remarkable ability suppress NF-kB-mediated by inhibiting cytokines TNF-α IL-6. Additionally, restored antioxidant enzymes, catalase glutathione peroxidase, thereby counteracting stress. Notably, modulated regulators, caspase, Bcl2, Bax, suggesting role regulating programmed cell death. These biochemical alterations consistent with improved structural integrity as revealed histological examination. In comparison, exhibited lower efficacy at an equivalent dosage. Liposomal shows promise alleviating hyperglycemia-induced diabetes. Further research warranted explore agent possible effects.

Language: Английский

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Multi-target approach to Alzheimer’s disease prevention and treatment: antioxidant, anti-inflammatory, and amyloid- modulating mechanisms

Neurogenetics, Journal Year: 2025, Volume and Issue: 26(1)

Published: April 1, 2025

Language: Английский

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Selective imaging probes for differential detection of pathological tau polymorphs in tauopathies

Drug Discovery Today, Journal Year: 2025, Volume and Issue: unknown, P. 104352 - 104352

Published: April 1, 2025

Tauopathies, including Alzheimer's disease (AD), Pick's (PiD), progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD), are characterized by the misfolding pathological aggregation of tau protein, leading to neurodegeneration. Although pathogenesis these diseases is still a matter for debate, formation amyloid inclusions represents only histopathological hallmark available. Tau not same in terms structure morphology, different tauopathies polymorphs. Remarkably, selective detection polymorphs crucial differential diagnosis, monitoring evaluation potential harmfulness polymorphs, with significant impact on drug discovery. This review discusses recent advances development imaging probes designed forms associated specific tauopathies. We explore application compounds that can target characteristic AD, PiD, PSP CBD. In particular, we focus discussing probes' selectivity sensitivity distinguishing between tauopathy-associated preclinical settings. The progress weaknesses this field discussed, guide researchers identifying accurate potent diagnosis neurodegenerative diseases.

Language: Английский

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Osthole's capacity to prevent tau aggregation, a key protein in tauopathy and Alzheimer's disease

International Journal of Biological Macromolecules, Journal Year: 2025, Volume and Issue: unknown, P. 143235 - 143235

Published: April 1, 2025

Language: Английский

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Acetylcholinesterase Inhibitory Potential of Plant-Based Phenolics in the Treatment of Alzheimer's Disease: An In Silico Approach

Research Square (Research Square), Journal Year: 2025, Volume and Issue: unknown

Published: May 7, 2025

Alzheimer's disease is the most prevalent cause of dementia, accounting for more than seventy per cent all reported cases. Among various treatment strategies, inhibiting action acetylcholinesterase that breaks down neurotransmitter acetylcholine common. In this report, thirty-eight phenolic compounds were retrieved from PubChem database and screened in silico against acetylcholinesterase. Non-covalent molecular docking, mechanics-generalized born surface area (MM-GBSA), dynamics (MD) used to predict their binding mode, affinity, free energy, stability protein-ligand complex. These followed by drug-likeness screening a rigorous prediction absorption, distribution, metabolism, excretion, toxicity (ADMET) parameters. Myricetin (-13.9 kcal/mol) was predicted have highest affinity among phenolics, though lower bound donepezil (-16.3 kcal/mol). To increase myricetin, it modified via Schiff base formation, which gave hydrazine B-1 -17.7 kcal/mol, higher donepezil. The simulation showed ligands better myricetin. ADMET studies top four phenolics myricetin analogue derivatives could be further developed as potential drug candidates.

Language: Английский

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