Natural acetylcholinesterase inhibitors: A multi-targeted therapeutic potential in Alzheimer's disease

European Journal of Medicinal Chemistry Reports, Journal Year: 2024, Volume and Issue: 11, P. 100154 - 100154

Published: April 7, 2024

Alzheimer's disease (AD), the main dementia type accounting for over 70 % of entire population, progressive decline in memory and executive function. AD pathology is characterized by amyloid fibrils neurofibrillary tangles. Acetylcholinesterase (AChE), an enzyme involved hydrolysis neurotransmitter acetylcholine, consistently colocalizes with deposits characteristic may contribute to generation proteins. AChE a potent amyloid-promoting factor when compared other c-associated inhibitors play vital role prevent formation toxic oligomeric form peptide. Recent studies have reported that acetylcholinesterase (ChE-Is) are present plants, fungi, marine products. Some cholinesterase inhibitors, obtained from plant source such as rivastigmine, donepezil, galantamine, used treatment AD, offer alternative approach alleviate its symptoms reducing Aβ. Due limited efficacy current drugs there huge potential phytomedicines AD. Medicinal herbs herbal drug preparations traditionally been treat neurological disorders exhibiting anti-inflammatory neuroprotective properties. Phytomedicines containing flavonoids, polyphenols, naturally occurring antioxidants crosses blood-brain barrier protect neurons oxidative stress. As synthetic drugs, fewer side effects. Therefore, recent research focused explore develop it effective In our review, we summarized amyloid-deposition, Acetylcholinesterase, phytoconstituents inhibitory activity treatment.

Language: Английский

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DeepDrug as an expert guided and AI driven drug repurposing methodology for selecting the lead combination of drugs for Alzheimer’s disease

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: Jan. 15, 2025

Language: Английский

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Lipidome disruption in Alzheimer’s disease brain: detection, pathological mechanisms, and therapeutic implications

Molecular Neurodegeneration, Journal Year: 2025, Volume and Issue: 20(1)

Published: Jan. 27, 2025

Alzheimer's disease (AD) is among the most devastating neurodegenerative disorders with limited treatment options. Emerging evidence points to involvement of lipid dysregulation in development AD. Nevertheless, precise lipidomic landscape and mechanistic roles lipids pathology remain poorly understood. This review aims highlight significance lipidomics lipid-targeting approaches diagnosis We summarized connection between human brain AD at both genetic species levels. briefly introduced technologies discussed potential challenges areas future advancements field for research. To elucidate central role converging multiple pathological aspects AD, we reviewed current knowledge on interplay major features, including amyloid beta, tau, neuroinflammation. Finally, assessed progresses obstacles lipid-based therapeutics proposed strategies leveraging

Language: Английский

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The Role of Glial Cell Senescence in Alzheimer's Disease

Journal of Neurochemistry, Journal Year: 2025, Volume and Issue: 169(3)

Published: March 1, 2025

Glial cell senescence, characterized by the irreversible arrest of division and a pro-inflammatory secretory phenotype, has emerged as critical player in pathogenesis Alzheimer's disease (ad). While much attention been devoted to role neurons ad, growing evidence suggests that glial cells, including astrocytes, microglia, oligodendrocytes, contribute significantly progression through senescence. In this review, we explore molecular mechanisms underlying senescence focusing on cellular signaling pathways, DNA damage response accumulation senescence-associated phenotypes (SASP). We also examine how senescent cells exacerbate neuroinflammation, disrupt synaptic function, promote neuronal death ad. Moreover, discuss emerging therapeutic strategies aimed at targeting mitigate neurodegenerative processes By providing comprehensive overview current research disease, review highlights its potential novel target fight against

Language: Английский

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Oxidative Stress and Redox Imbalance: Common Mechanisms in Cancer Stem Cells and Neurodegenerative Diseases

Cells, Journal Year: 2025, Volume and Issue: 14(7), P. 511 - 511

Published: March 29, 2025

Oxidative stress (OS) is an established hallmark of cancer and neurodegenerative disorders (NDDs), which contributes to genomic instability neuronal loss. This review explores the contrasting role OS in stem cells (CSCs) NDDs. Elevated levels reactive oxygen species (ROS) contribute promote tumor initiation progression CSCs, while NDDs such as Alzheimer’s Parkinson’s disease, accelerates death impairs cellular repair mechanisms. Both scenarios involve disruption delicate balance between pro-oxidant antioxidant systems, leads chronic oxidative stress. Notably, CSCs neurons display alterations redox-sensitive signaling pathways, including Nrf2 NF-κB, influence cell survival, proliferation, differentiation. Mitochondrial dynamics further illustrate these differences: enhanced function supports adaptability whereas impairments heighten vulnerability. Understanding common mechanisms OS-induced redox imbalance may provide insights for developing interventions, addressing aging hallmarks, potentially mitigating or preventing both

Language: Английский

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Proteostasis disruption and senescence in Alzheimer’s disease pathways to neurodegeneration

Brain Research, Journal Year: 2024, Volume and Issue: 1845, P. 149202 - 149202

Published: Aug. 30, 2024

Language: Английский

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Hallmarks of aging and Alzheimer’s Disease pathogenesis: paving the route for new therapeutic targets

Ageing Research Reviews, Journal Year: 2025, Volume and Issue: 106, P. 102699 - 102699

Published: Feb. 20, 2025

Language: Английский

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Role of autophagy and proteostasis in neurodegenerative diseases: Exploring the therapeutic interventions

Chemical Biology & Drug Design, Journal Year: 2024, Volume and Issue: 103(4)

Published: April 1, 2024

Abstract Neurodegenerative disorders are devastating characterized by gradual loss of neurons and cognition or mobility impairment. The common pathological features these diseases associated with the accumulation misfolded aggregation proteins. pivotal roles autophagy proteostasis in maintaining cellular health preventing proteins, which neurodegenerative like Huntington's disease (HD), Alzheimer's (AD), Parkinson's (PD). This article presents an in‐depth examination interplay between proteostasis, highlighting how processes cooperatively contribute to homeostasis prevent pathogenic protein aggregate accumulation. Furthermore, review emphasises potential therapeutic implications targeting mitigate diseases. While advancements research hold promise for developing novel treatments, also addresses challenges complexities modulating intricate pathways. Ultimately, advancing understanding underlying mechanism provides valuable insights into avenues future directions.

Language: Английский

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Senescence and Neurodegenerative Disorders: Beyond Alzheimer’s and Parkinson’s

Published: Jan. 1, 2025

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Unlocking the Neuroprotective Potential of Silymarin: A Promising Ally in Safeguarding the Brain from Alzheimer’s Disease and Other Neurological Disorders

Molecular Neurobiology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 17, 2025

Language: Английский

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