New Insights into the Development of Donepezil-Based Hybrid and Natural Molecules as Multi-Target Drug Agents for Alzheimer’s Disease Treatment DOI Creative Commons
Violina T. Angelova, Boris Petrov Stoyanov, Rumyana Simeonova

et al.

Molecules, Journal Year: 2024, Volume and Issue: 29(22), P. 5314 - 5314

Published: Nov. 11, 2024

Alzheimer's disease (AD) involves a complex pathophysiology with multiple interconnected subpathologies, including protein aggregation, impaired neurotransmission, oxidative stress, and microglia-mediated neuroinflammation. Current treatments, which generally target single subpathology, have failed to modify the disease's progression, providing only temporary symptom relief. Multi-target drugs (MTDs) address several aggregation of pathological proteins. In this review, we cover hybrid molecules published between 2014 2024. We offer an overview strategies employed in drug design approaches that led notable improvements reduced hepatotoxicity. Our aim is insights into potential development new drugs. This highlights multi-target featuring heterocycles

Language: Английский

Safety issues of donepezil combined with memantine in Alzheimer’s disease population: real-world pharmacovigilance DOI
Yi Zeng,

Bingshuo Liu,

Lisi Zhou

et al.

Expert Opinion on Drug Safety, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 14, 2025

Alzheimer's disease (AD) is the most common form of dementia. The combination Donepezil and Memantine only FDA-approved therapy for AD, but its adverse drug reactions (ADRs) lack systematic analysis. This study carried out analysis AD population to provide evidence support clinical safety use. Using FAERS database reports (January 2004-January 2024) with as primary suspected drugs, four disproportionality methods - ROR, PRR, BCPNN, EBGM were applied identify positive ADR signals. Subgroup analyses conducted by age gender. A total 712 analyzed (54.6% female, 55.1% aged 65-85). Across population, 42 ADRs identified, including hypertensive crisis, hyperglycemia, hyperosmolar nonketotic syndrome, proteinuria, hydronephrosis, many which newly reported. revealed prostate hypertrophy, acute kidney injury, cerebral infarction in males, while females experienced more severe cardiovascular events, such complete AV block ventricular extrasystole. Additional included hyperkalemia, sinus bradycardia, extrapyramidal disorders. Despite partial consistency combined instructions, new signals emerged, significant differences subgroups.

Language: Английский

Citations

1
Antarctic Krill Protein Amyloid Fibrils as a Novel Iron Carrier for the Improvement of Iron Deficiency DOI

Xueqing He,

Songyi Lin,

Lei Chen

et al.

Journal of Agricultural and Food Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 24, 2025

Iron fortification with food supplements remains the primary dietary strategy for improving iron deficiency anemia (IDA). This study used Antarctic krill protein fibrillar design to form an amyloid fibril (AKAF). The results indicated that peptides generated by proteolysis were a prerequisite assembly, forming elongated structures and cross-linking upon heating. During this process, hydrogen bonds rearranged, ordered β-sheet conformations (49.36 ± 0.21%); π–π stacking interactions among aromatic residues contributed formation. Further studies showed AKAF effectively maintained in bioavailable state exhibited high binding capacity (60.67 0.69%). Moreover, AKAF-iron complex markedly ameliorated hematological abnormalities IDA mice, enhanced storage liver spleen, positively influenced expression of homeostasis genes. was also effective alleviating gastric inflammatory responses induced IDA. Overall, holds promise as efficient delivery carrier.

Language: Английский

Citations

0
Influence of immune cells and inflammatory factors on Alzheimer’s disease axis: evidence from mediation Mendelian randomization study DOI Creative Commons

Linzhu,

Jianxin Zhang,

Wenhui Fan

et al.

BMC Neurology, Journal Year: 2025, Volume and Issue: 25(1)

Published: Feb. 5, 2025

Alzheimer's disease (AD) is one of the most common forms dementia in elderly, characterized by progressive neurodegeneration. While exact etiology AD remains unclear, immune inflammation known to play a significant role disease. This study utilized two-sample Mendelian randomization (MR) approach assess causal relationship between different types cells and AD, while considering inflammatory factors as intermediate variables. Data were collected from three sources: cell data (731 phenotypes), (48 cytokines 8,293 individuals), (35,274 cases, 59,163 controls). Multiple MR methods employed minimize bias, detailed descriptions instrumental variable selection statistical provided. The findings suggest potential relationships six well 13 factors. Additionally, two statistically found have with AD. Specifically, CD33-HLA DR + CD45 on may further influence regulating Interleukin-2 levels. provides valuable insights into immunoinflammatory pathogenesis offers partial guidance for development relevant interventions, thereby contributing beneficial information prevention treatment related diseases.

Language: Английский

Citations

0
Critical role of Oas1g and STAT1 pathways in neuroinflammation: insights for Alzheimer’s disease therapeutics DOI Creative Commons
Zhixin Xie, Linxi Li,

Weizhong Hou

et al.

Journal of Translational Medicine, Journal Year: 2025, Volume and Issue: 23(1)

Published: Feb. 14, 2025

Alzheimer's disease (AD) has a significant impact on an individual's health and places heavy burden society. Studies have emphasized the importance of microglia in progression development AD. Interferon responses Interferon-stimulated genes (ISGs) significantly function neuroinflammatory neurodegenerative diseases involving Therefore, further exploration relationship among microglia, ISGs, neuroinflammation AD is warranted. Microglia datasets from GEO database were retrieved, along with additional RNA-seq data laboratory mice. Weighted Correlation Network Analysis was used training dataset to identify gene co-expression networks. Genes black module intersected interferon-stimulated genes, differentially expressed (DEGs) identified. Machine learning algorithms applied DEGs, selected by both methods identified as hub ROC curves evaluate their diagnostic accuracy. Gene Set Enrichment performed reveal functional pathways closely relating genes. cells transfected siRNAs targeting Oas1g STAT1. Total RNA mouse brain tissues extracted, reverse-transcribed, analyzed via qRT-PCR. Proteins extracted cells, quantified, separated SDS-PAGE, transferred PVDF membranes, probed antibodies. fixed, permeabilized, blocked, stained antibodies for STAT1, then visualized photographed. Bioinformatics machine revealed that gene, AUC 0.812. associated interferon-related pathways. Expression validated models, where it upregulated after microglial activation. Knockdown experiments suggested siOas1g attenuated effect siSTAT1, expressions STAT1 p-STAT1 elevated. could reverse indicating potentially regulates ISGs through pathway. We demonstrated ISG can downregulate activation IFN-β reducing expression neuroinflammation. might be beneficial candidate prevention treatment

Language: Английский

Citations

0
Design, synthesis of 2-phenyl-1H-benzo[d]imidazole derivatives as 17β-HSD10 inhibitor for the treatment of Alzheimer's Disease DOI
Xiaohan Liu, Bin Zhou, Yan Chen

et al.

RSC Medicinal Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

It has been reported that 17β-HSD10 plays a key role in Alzheimer's disease. Here, total of 44 2-phenyl-1H-benzo[d]imidazole derivatives were designed and synthesized as novel inhibitors based on rational design SAR studies. Among them, compound 33 (N-(4-(1,4,6-trimethyl-1H-benzo[d] imidazol-2-yl)phenyl)cyclohexanecarboxamide) showed high inhibitory efficacy (17β-HSD10 IC50 = 1.65 ± 0.55 μM) low toxicity (HepaRG >100 μM). The Morris water maze experiment revealed could alleviate cognitive impairment induced by scopolamine mice. This study facilitates the further development more potent for treatment

Language: Английский

Citations

0
Natural Bioactive Compounds Solanesol and Chlorogenic Acid Assembled Nanomicelles for Alzheimer’s Disease Therapy DOI
Chenchen Wang, Xiaowan Zhang,

Yurong Zhuang

et al.

ACS Applied Materials & Interfaces, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 25, 2025

Solanesol (Sol) and chlorogenic acid (CHA) are naturally active compounds. Sol exhibits a significant free radical absorption ability strong antioxidant activity. CHA, typical phenolic acid, excellent anticancer, anti-inflammation, antibacterial properties. Herein, bifunctional nanomicelles (CI@SPK) were skillfully designed to take advantage of the unique properties CHA treat Alzheimer's disease (AD). Hydrophobic was modified with poly(ethylene glycol) self-assemble into stable (SP). could be encapsulated hydrophobic core these nanomicelles, which increased its bioavailability greatly. Short peptide K (CKLVFFAED) incorporated facilitate their crossing blood-brain barrier. Then, CI@SPK targeted AD lesion area, released in greater quantities help IR780 under irradiation an 808 nm laser, resulting synergistically scavenging reactive oxygen species (ROS) Sol. Consequently, demonstrated capabilities ROS, inhibiting β-amyloid (Aβ) aggregation, eventually modulating microglia phenotype from M1 M2 promote Aβ phagocytosis clearance. In vivo studies indicated that improved learning cognitive impairments APP/PS1 mice by reducing plaque inflammation, signifying potential value clinical application for treatment.

Language: Английский

Citations

0
Neuroadaptation in neurodegenerative diseases: compensatory mechanisms and therapeutic approaches DOI

Spandana Rajendra Kopalli,

Tapan Behl, Lalji Baldaniya

et al.

Progress in Neuro-Psychopharmacology and Biological Psychiatry, Journal Year: 2025, Volume and Issue: 139, P. 111375 - 111375

Published: April 23, 2025

Language: Английский

Citations

0
Advances in biosensors for diagnosis of Alzheimer’s and Parkinson’s diseases DOI
Masoud Negahdary, Indherjith Sakthinathan, Ensiyeh Mirsadoughi

et al.

Biosensors and Bioelectronics, Journal Year: 2025, Volume and Issue: unknown, P. 117535 - 117535

Published: May 1, 2025

Language: Английский

Citations

0
Intrathecal Immunoselective Nanopheresis for Alzheimer’s Disease: What and How? Why and When? DOI Open Access
Manuel Menéndez‐González

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(19), P. 10632 - 10632

Published: Oct. 2, 2024

Nanotechnology is transforming therapeutics for brain disorders, especially in developing drug delivery systems. Intrathecal immunoselective nanopheresis with soluble monoclonal antibodies represents an innovative approach the realm of systems Central Nervous System conditions, targeting beta-amyloid Alzheimer’s disease. This review delves into concept intrathecal nanopheresis. It provides overall description devices to perform this technique while discussing nanotechnology behind its mechanism action, potential advantages, and clinical implications. By exploring current research advancements, we aim provide a comprehensive understanding novel method, addressing critical questions what it is, how works, why needed, when should be applied. Special attention given patient selection optimal timing therapy initiation Alzheimer’s, coinciding peak accumulation amyloid oligomers early stages. Potential limitations alternative targets beyond future perspectives are also described.

Language: Английский

Citations

2
New Insights into the Development of Donepezil-Based Hybrid and Natural Molecules as Multi-Target Drug Agents for Alzheimer’s Disease Treatment DOI Creative Commons
Violina T. Angelova, Boris Petrov Stoyanov, Rumyana Simeonova

et al.

Molecules, Journal Year: 2024, Volume and Issue: 29(22), P. 5314 - 5314

Published: Nov. 11, 2024

Alzheimer's disease (AD) involves a complex pathophysiology with multiple interconnected subpathologies, including protein aggregation, impaired neurotransmission, oxidative stress, and microglia-mediated neuroinflammation. Current treatments, which generally target single subpathology, have failed to modify the disease's progression, providing only temporary symptom relief. Multi-target drugs (MTDs) address several aggregation of pathological proteins. In this review, we cover hybrid molecules published between 2014 2024. We offer an overview strategies employed in drug design approaches that led notable improvements reduced hepatotoxicity. Our aim is insights into potential development new drugs. This highlights multi-target featuring heterocycles

Language: Английский

Citations

0