Alzheimer's disease is currently thought to be a complex, multifactorial syndrome, unlikely to arise from a single causal factor; instead, a number of related biological alterations are thought to contribute to its pathogenesis. This may explain why the currently available drugs, developed according to the classic drug discovery paradigm of "one-molecule-one-target," have turned out to be palliative. In light of this, drug combinations that can act at different levels of the neurotoxic cascade offer new avenues toward curing Alzheimer's and other neurodegenerative diseases. In parallel, a new strategy is emerging-that of developing a single chemical entity able to modulate multiple targets simultaneously. This has led to a new paradigm in medicinal chemistry, the "multi-target-directed ligand" design strategy, which has already been successfully exploited at both academic and industrial levels. As a case study, we report here on memoquin, a new molecule developed following this strategy. The in vitro and in vivo biological profile of memoquin demonstrates the suitability of the new strategy for obtaining innovative drug candidates for the treatment of neurodegenerative diseases.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5084263 | PMC |
| http://dx.doi.org/10.1016/j.nurt.2008.10.042 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Lateralization of the Aberrant Amplitude of Low-Frequency Fluctuation within the Default Mode Network in Patients with Mild Cognitive Impairment.
Acad Radiol
January 2025
Department of Radiology, Eye & ENT Hospital of Fudan University, 83 Fenyang Road, Shanghai 200031, China (Q.X.). Electronic address:
Rationale And Objectives: Alzheimer's disease (AD) is the most common pathogenesis of dementia, and mild cognitive impairment (MCI) is considered as the intermediate stage from normal elderly to AD. Early detection of MCI is an essential step for the timely intervention of AD to slow the progression of this disease. Different form previous studies in the whole-brain spontaneous activities, this research aimed to explore the low-frequency amplitude spectrum activities of patients with MCI within the default mode network (DMN), which has been involved in the process of maintaining normal cognitive function.
View Article and Find Full Text PDFPhosphorylated-tau associates with HSV-1 chromatin and correlates with nuclear speckles decondensation in low-density host chromatin regions.
Neurobiol Dis
January 2025
Department of Molecular Genetics & Microbiology, University of Florida College of Medicine, Gainesville, FL 32611, USA.
Abnormal tau phosphorylation is a key mechanism in neurodegenerative diseases. Evidence implicates infectious agents, such as Herpes Simplex Virus 1 (HSV-1), as co-factors in the onset or the progression of neurodegenerative diseases, including Alzheimer's disease. This has led to divergence in the field regarding the contribution of viruses in the etiology of neurodegenerative diseases.
View Article and Find Full Text PDFExposure to nano-polystyrene during pregnancy leads to Alzheimer's disease-related pathological changes in adult offspring.
Ecotoxicol Environ Saf
January 2025
Department of Occupational Medicine and Environmental Toxicology, Nantong Key Laboratory of Environmental Toxicology, School of Public Health, Nantong University, Nantong 226019, China. Electronic address:
Nanoplastics are common environmental pollutants. As of now, research has yet to explore how exposure to nanomaterials during gestation might influence the risk of developing Alzheimer's disease (AD) in offspring. Throughout the research, we assessed the AD pathology in adult offspring of mice prenatal 80 nm polystyrene nanoparticles (PS-NPs) exposure.
View Article and Find Full Text PDFDevelopment of multifunctional fluorescence-emitting potential theranostic agents for Alzheimer's disease.
Talanta
January 2025
Pharmaceutical Chemistry Research Laboratory I, Department of Pharmaceutical Engineering & Technology, Indian Institute of Technology (Banaras Hindu University), Varanasi, 221005, India. Electronic address:
The cholinergic deficits and amyloid beta (Aβ) aggregation are the mainstream simultaneously observed pathologies during the progression of Alzheimer's disease (AD). Deposited Aβ plaques are considered to be the primary pathological hallmarks of AD and are contemplated as promising diagnostic biomarker. Herein, a series of novel theranostic agents were designed, synthesised and evaluated against cholinesterase (ChEs) enzymes and detection of Aβ species, which are major targets for development of therapeutics for AD.
View Article and Find Full Text PDFHEBE: A novel chimeric chronokine for ameliorating memory deficits in Alzheimer's disease.
Biomed Pharmacother
January 2025
Institut de Neurociències (INc), Universitat Autònoma Barcelona, Bellaterra 08193, Spain; Vall d'Hebron Institut de Recerca (VHIR), Barcelona 08035, Spain; Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona 08010, Spain. Electronic address:
Alzheimer's disease (AD) is a prevalent neurodegenerative disorder characterized by amyloid-β and Tau protein depositions, with treatments focusing on single proteins have shown limited success due to the complexity of pathways involved. This study explored the potential of chronokines -proteins that modulate aging-related processes- as an alternative therapeutic approach. Specifically, we focused on a novel pleiotropic chimeric protein named HEBE, combining s-KL, sTREM2 and TIMP2, guided by bioinformatic analyses to ensure the preservation of each protein's conformation, crucial for their functions.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!