Indole-3 Carbinol and Diindolylmethane Mitigated β-Amyloid-Induced Neurotoxicity and Acetylcholinesterase Enzyme Activity: In Silico, In Vitro, and Network Pharmacology Study

Diseases, Journal Year: 2024, Volume and Issue: 12(8), P. 184 - 184

Published: Aug. 16, 2024

Background: Alzheimer’s disease (AD) is a neurodegenerative characterized by beta-amyloid (Aβ) deposition and increased acetylcholinesterase (AchE) enzyme activities. Indole 3 carbinol (I3C) diindolylmethane (DIM) are reported to have neuroprotective activities against various neurological diseases, including ischemic stroke, Parkinson’s disease, neonatal asphyxia, depression, stress, neuroinflammation, excitotoxicity, except for AD. In the present study, we investigated anti-AD effects of I3C DIM. Methods: Docking molecular dynamic studies AchE network pharmacological were conducted DIM’s self AchE-induced Aβ aggregation investigated. The DIM Aβ-induced neurotoxicity assessed in SH-S5Y5 cells observing cell viability ROS. Results: with show binding efficiency −7.0 −10.3, respectively, dynamics revealed better interaction stability between AchE. Network indicated that interacted several proteins involved pathophysiology Further, significantly inhibited (IC50: (18.98 µM) (11.84 µM)) self-induced aggregation. Both compounds enhanced exposed reduced equipotential neuroprotection when compared donepezil. Conclusions: Our findings indicate both inhibiting induced

Language: Английский

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Exosomes as therapeutic and drug delivery vehicle for neurodegenerative diseases

Journal of Nanobiotechnology, Journal Year: 2024, Volume and Issue: 22(1)

Published: Aug. 2, 2024

Abstract Neurodegenerative disorders are complex, progressive, and life-threatening. They cause mortality disability for millions of people worldwide. Appropriate treatment neurodegenerative diseases (NDs) is still clinically lacking due to the presence blood-brain barrier (BBB). Developing an effective transport system that can cross BBB enhance therapeutic effect neuroprotective agents has been a major challenge NDs. Exosomes endogenous nano-sized vesicles naturally carry biomolecular cargoes. Many studies have indicated exosome content, particularly microRNAs (miRNAs), possess biological activities by targeting several signaling pathways involved in apoptosis, inflammation, autophagy, oxidative stress. Exosome content influence cellular function healthy or pathological ways. Furthermore, since exosomes reflect features parental cells, their cargoes offer opportunities early diagnosis intervention diseases. unique characteristics make them ideal delivering drugs directly brain. These include ability pass through BBB, biocompatibility, stability, innate properties. This review emphasizes role alleviating NDs discusses associated molecular mechanisms. exosomes, making promising natural transporter various medications brain combat NDs, also discussed.

Language: Английский

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An Update of Fungal Endophyte Diversity and Strategies for Augmenting Therapeutic Potential of their Potent Metabolites: Recent Advancement

Applied Biochemistry and Biotechnology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 5, 2025

Abstract Endophytic fungi represent a significant renewable resource for the discovery of pharmaceutically important compounds, offering substantial potential new drug development. Their ability to address growing issue resistance has drawn attention from researchers seeking novel, nature-derived lead molecules that can be produced on large scale meet global demand. Recent advancements in genomics, metabolomics, bioinformatics, and improved cultivation techniques have significantly aided identification characterization fungal endophytes their metabolites. Current estimates suggest there are approximately 1.20 million globally, yet only around 16% (190,000) been identified studied detail. This underscores vast untapped pharmaceutical research. Research increasingly focused transformation bioactive compounds by through chemical enzymatic processes. A notable example is anthraquinone derivative 6-O-methylalaternin, whose cytotoxic enhanced addition hydroxyl group, sharing structural similarities with its parent compound macrosporin. These structure-bioactivity studies open up avenues developing safer more effective therapeutic agents synthesizing targeted derivatives. Despite immense promise, challenges remain, particularly large-scale understanding complexities biosynthetic pathways. Additionally, genetic manipulation optimized metabolite production still infancy. Future research should aim overcome these limitations focusing efficient methods deeper exploration endophytes’ metabolic capabilities fully harness potential. Graphical

Language: Английский

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Mitochondrial Dysfunction in Alzheimer’s Disease

Ageing Research Reviews, Journal Year: 2025, Volume and Issue: unknown, P. 102713 - 102713

Published: Feb. 1, 2025

Language: Английский

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Relationship between enriched environment and neurodegeneration: a review from mechanism to therapy

Clinical Epigenetics, Journal Year: 2025, Volume and Issue: 17(1)

Published: Jan. 24, 2025

Enriched environment (EE), as a non-pharmacological intervention, has garnered considerable attention for its potential to ameliorate neurodegenerative diseases (NDs). This review delineated the impact of EE on biological functions associated with NDs, emphasizing role in enhancing neural plasticity, reducing inflammation, and bolstering cognitive performance. We discussed molecular underpinnings effects EE, including modulation key signaling pathways such extracellular regulated kinase 1/2 (ERK1/2), mitogen-activated protein kinases (MAPK), AMPK/SIRT1, which were implicated neuroprotection synaptic plasticity. Additionally, we scrutinized influence epigenetic modifications autophagy, processes pivotal ND pathogenesis. Animal models, encompassing both rodents larger animals, offer insights into disease-modifying underscoring complementary approach pharmacological interventions. In summary, emerges promising strategy augment function decelerate progression NDs.

Language: Английский

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Heavy metal-induced disruption of the autophagy-lysosomal pathway: implications for aging and neurodegenerative disorders

BioMetals, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 17, 2025

Language: Английский

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Klotho antiaging protein: molecular mechanisms and therapeutic potential in diseases

Molecular Biomedicine, Journal Year: 2025, Volume and Issue: 6(1)

Published: March 22, 2025

Abstract Klotho, initially introduced as an anti-aging protein, is expressed in the brain, pancreas, and most prominently kidney. The two forms of Klotho (membrane-bound soluble form) have diverse pharmacological functions such anti-inflammatory, anti-oxidative, anti-fibrotic, tumour-suppressive etc. membrane-bound form plays a pivotal role maintaining kidney homeostasis by regulating fibroblast growth factor 23 (FGF 23) signalling, vitamin D metabolism phosphate balance. deficiency has been linked with significantly reduced protection against various pathological phenotypes, including diabetic disease (DKD), which major cause chronic leading to end-stage disease. Owing pleiotropic actions klotho, it shown beneficial effects DKD tackling complex pathophysiology reducing inflammation, oxidative stress, well fibrosis. Moreover, protective effect klotho extends beyond other conditions, cardiovascular diseases, alzheimer's disease, cancer, inflammatory bowel liver Therefore, this review summarizes relationship between expression diseases special emphasis on DKD, distinct mechanisms potential exogenous supplementation therapeutic strategy. Future research into could unravel novel treatment avenues for diseases.

Language: Английский

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A comprehensive review of advanced focused ultrasound (FUS) microbubbles-mediated treatment of Alzheimer’s disease

Heliyon, Journal Year: 2024, Volume and Issue: 10(18), P. e37533 - e37533

Published: Sept. 1, 2024

Language: Английский

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Insights Into the Therapeutic Potential of SIRT1-modifying Compounds for Alzheimer’s Disease: A Focus on Molecular Mechanisms

Journal of Molecular Neuroscience, Journal Year: 2025, Volume and Issue: 75(1)

Published: Feb. 25, 2025

Language: Английский

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Advanced strategies for enhancing the neuroprotective potential of curcumin: delivery systems and mechanistic insights in neurodegenerative disorders

Nutritional Neuroscience, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 26

Published: March 3, 2025

Background: Curcumin, a polyphenolic compound derived from Curcuma longa, exhibits significant neuroprotective potential due to its diverse pharmacological properties.Objective: This review explores curcumin's role in modulating key pathological mechanisms underlying neurodegenerative disorders such as Alzheimer's, Parkinson's diseases, Amyotrophic Lateral Sclerosis, Huntington's Disease and Prion Disease.Methods: A comprehensive analysis of molecular interactions, including effects on amyloid-beta (Aβ) aggregation, tau hyperphosphorylation, neuroinflammation, oxidative stress, metal-induced neurotoxicity, was conducted. Additionally, strategies overcome low bioavailability blood-brain barrier (BBB) permeability were evaluated.Results: Curcumin inhibits Aβ aggregation promotes disaggregation, reducing amyloid plaque formation Alzheimer's disease. It modulates glial cell activity, attenuating neuroinflammation fostering environment. By interacting with proteins, curcumin prevents hyperphosphorylation neurofibrillary tangle formation. As potent antioxidant, it scavenges reactive oxygen species, mitigating stress-related neuronal damage. Its metal-chelating properties further diminish neurotoxicity by sequestering iron copper ions. Despite limited BBB permeability, therapeutic efficacy can be enhanced using nanocarriers nanoparticles, liposomes, micelles, which improve solubility, stability, brain penetration.Conclusion: Curcumin's multifaceted make promising candidate for preventing or slowing disease progression. Advanced drug delivery systems hold overcoming pharmacokinetic limitations, paving the way future clinical applications.

Language: Английский

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