A series of novel styryl dye derivatives incorporating indolium and quinolinium core structures were successfully synthesized to explore their interacting and binding capabilities with tau aggregates in vitro and in cells. The synthesized dyes exhibited enhanced fluorescence emission in viscous environments due to the rotatable bond confinement in the core structure. Dye 4, containing a quinolinium moeity and featuring two cationic sites, demonstrated a 28-fold increase in fluorescence emission upon binding to tau aggregates. This dye could also stain tau aggregates in living cells, confirmed by cell imaging using confocal fluorescence microscopy. A molecular docking study was conducted to provide additional visualization and support for binding interactions. This work offers novel and non-cytotoxic fluorescent probes with desirable photophysical properties, which could potentially be used for studying tau aggregates in living cells, prompting further development of new fluorescent probes for early Alzheimer's disease detection.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1002/asia.202301081 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Recent advancements in the therapeutic approaches for Alzheimer's disease treatment: current and future perspective.
RSC Med Chem
December 2024
Pharmaceutical Chemistry Research Laboratory, Department of Pharmacy, Birla Institute of Technology and Sciences Pilani Pilani Campus, Vidya Vihar Pilani 333031 RJ India +91 1596 244183 +91 1596 255 506.
Alzheimer's disease (AD) is a complex, incurable neurological condition characterized by cognitive decline, cholinergic neuron reduction, and neuronal loss. Its exact pathology remains uncertain, but multiple treatment hypotheses have emerged. The current treatments, single or combined, alleviate only symptoms and struggle to manage AD due to its multifaceted pathology.
View Article and Find Full Text PDFBiomarker Detection and Therapy of Parkinson's and Alzheimer's disease using upconversion based approach: A Comprehensive Review.
Ageing Res Rev
January 2025
Department of Pharmaceutics, NIMS Institute of Pharmacy, NIMS University, Jaipur 303121, Rajasthan, India.
Neurodegenerative diseases (NDs) are debilitating disorders characterized by the progressive and selective loss of function or structure in the brain and spinal cord. Both chronic and acute forms of these diseases are associated with significant morbidity and mortality, as they involve the degeneration of neurons in various brain regions. Misfolding and aggregation of amyloid proteins into oligomer and β-sheet rich fibrils share as common hallmark and lead to neurotoxicity.
View Article and Find Full Text PDFPseudo-Phosphorylated Tau Forms Paired Helical Filaments in the Presence of High-Curvature Cholesterol-Containing Lipid Membranes.
J Am Chem Soc
January 2025
Department of Chemistry, Massachusetts Institute of Technology, 170 Albany Street, Cambridge, Massachusetts 02139, United States.
The tau protein misfolds in neurodegenerative diseases such as Alzheimer's disease (AD). These pathological tau aggregates are associated with neuronal membranes, but molecular structural information about how disease-like tau fibrils interact with the lipid membrane is scarce. Here, we use solid-state NMR to investigate the structure of a tau construct bearing four AD-relevant phospho-mimetic mutations (4E tau) with cholesterol-containing high-curvature lipid membranes, which mimic the membrane of synaptic vesicles in neurons.
View Article and Find Full Text PDFTubulin-Binding Region Modulates Cholesterol-Triggered Aggregation of Tau Proteins.
J Neurochem
January 2025
Department of Biochemistry and Biophysics, Texas A&M University, College Station, Texas, USA.
A hallmark of Alzheimer disease (AD) and tauopathies, severe neurodegenerative diseases, is the progressive aggregation of Tau, also known as microtubule-associated Tau protein. Full-length Tau, also known as 2N4R, contains two N-terminal inserts that bind to tubulin. This facilitates the self-assembly of tubulin simultaneously enhancing stability of cell microtubules.
View Article and Find Full Text PDFEssential tremor with tau pathology features seeds indistinguishable in conformation from Alzheimer's disease and primary age-related tauopathy.
Acta Neuropathol
January 2025
Center for Alzheimer's and Neurodegenerative Diseases, Peter O'Donnell Jr. Brain Institute, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Neurodegenerative tauopathies are characterized by the deposition of distinct fibrillar tau assemblies, whose rigid core structures correlate with defined neuropathological phenotypes. Essential tremor (ET) is a progressive neurological disorder that, in some cases, is associated with cognitive impairment and tau accumulation. In this study, we explored tau assembly conformation in ET patients with tau pathology using cytometry-based tau biosensor assays.
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!