The adenosine-triphosphate-(ATP)-binding cassette (ABC) transporter ABCA7 is a genetic risk factor for Alzheimer's disease (AD). Defective ABCA7 promotes AD development and/or progression. Unfortunately, ABCA7 belongs to the group of 'under-studied' ABC transporters that cannot be addressed by small-molecules. However, such small-molecules would allow for the exploration of ABCA7 as pharmacological target for the development of new AD diagnostics and therapeutics. Pan-ABC transporter modulators inherit the potential to explore under-studied ABC transporters as novel pharmacological targets by potentially binding to the proposed 'multitarget binding site'. Using the recently reported cryogenic-electron microscopy (cryo-EM) structures of ABCA1 and ABCA4, a homology model of ABCA7 has been generated. A set of novel, diverse, and potent pan-ABC transporter inhibitors has been docked to this ABCA7 homology model for the discovery of the multitarget binding site. Subsequently, application of pharmacophore modelling identified the essential pharmacophore features of these compounds that may support the rational drug design of innovative diagnostics and therapeutics against AD.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8666613 | PMC |
| http://dx.doi.org/10.1016/j.csbj.2021.11.035 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Characterization of cognitive decline in long-duration type 1 diabetes by cognitive, neuroimaging and pathological examinations.
JCI Insight
January 2025
Dianne Hoppes Nunnally Laboratory Research Division, Joslin Diabetes Center, Boston, United States of America.
Background: We aimed to characterize factors associated with the under-studied complication of cognitive decline in aging people with long-duration type 1 diabetes (T1D).
Methods: Joslin "Medalists" (n = 222; T1D ≥ 50 years) underwent cognitive testing. Medalists (n = 52) and age-matched non-diabetic controls (n = 20) underwent neuro- and retinal imaging.
Uncovering the intricacies of IGF-1 in Alzheimer's disease: new insights from regulation to therapeutic targeting.
Inflammopharmacology
January 2025
Neuropharmacology Division, Department of Pharmacology, ISF College of Pharmacy, Moga, 142001, Punjab, India.
Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by the accumulation of amyloid-β plaques and tau tangles, leading to cognitive decline and dementia. Insulin-like Growth Factor-1 (IGF-1) is similar in structure to insulin and is crucial for cell growth, differentiation, and regulating oxidative stress, synaptic plasticity, and mitochondrial function. IGF-1 exerts its physiological effects by binding to the IGF-1 receptor (IGF-1R) and activating PI3K/Akt pathway.
View Article and Find Full Text PDFDistinct Aggregation Behavior of -Terminally Truncated Aβ Over Aβ in the Presence of Zn(II).
ACS Chem Neurosci
January 2025
Department of Chemistry, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Republic of Korea.
The deposition of amyloid-β (Aβ) aggregates and metal ions within senile plaques is a hallmark of Alzheimer's disease (AD). Among the modifications observed in Aβ peptides, -terminal truncation at Phe4, yielding Aβ, is highly prevalent in AD-affected brains and significantly alters Aβ's metal-binding and aggregation profiles. Despite the abundance of Zn(II) in senile plaques, its impact on the aggregation and toxicity of Aβ remains unexplored.
View Article and Find Full Text PDFUsing Machine Learning to Design a FeMOF Bidirectional Regulator for Electrochemiluminescence Sensing of Tau Protein.
ACS Appl Mater Interfaces
January 2025
Key Laboratory of the Environmental Medicine and Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing 210009, China.
The single-luminophore-based ratiometric electrochemiluminescence (ECL) sensor coupling bidirectional regulator has become a research hotspot in the detection field because of its simplicity and accuracy. However, the limited bidirectional regulator hinders its further development. In this study, by leveraging the robust predictive capabilities of machine learning, we prepared an Fe-based metal-organic framework (FeMOF) as a bidirectional regulator for modulating the dual-emission ECL signals of a single luminophore for the first time.
View Article and Find Full Text PDFRedirecting Research to Alzheimer's Disease.
Cent Nerv Syst Agents Med Chem
January 2025
International Center of Neuroscience and Genomic Medicine, EuroEspes Biomedical Research Center, Corunna, Spain.
Want 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!