Polycatechols inhibit ferroptosis and modulate tau liquid-liquid phase separation to mitigate Alzheimer's disease.

Alzheimer's disease (AD) is a complex neurodegenerative disorder that affects learning, memory, and cognition. Current treatments targeting amyloid-β (Aβ) and tau have shown limited effectiveness, necessitating further research on the aggregation and toxicity mechanisms. One of these mechanisms involves the liquid-liquid phase separation (LLPS) of tau, contributing to the formation of pathogenic tau aggregates, although their conformational details remain elusive.

Biphasic modulation of tau liquid-liquid phase separation by polyphenols.

Molecular tools that modulate tau liquid-liquid phase separation (LLPS) promise to treat tauopathies. We screened a set of polyphenols and demonstrated concentration-dependent biphasic modulation of tau LLPS by gallic acid (GA), showcasing its ability to expedite the liquid-to-gel transition in tau condensates and effectively impede the formation of deleterious fibrillar aggregates.

Hybrid molecules synergistically mitigate ferroptosis and amyloid-associated toxicities in Alzheimer's disease.

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the build-up of extracellular amyloid β (Aβ) plaques and intracellular neurofibrillary tangles (NFTs). Ferroptosis, an iron (Fe)-dependent form of cell death plays a significant role in the multifaceted AD pathogenesis through generation of reactive oxygen species (ROS), mitochondrial damage, lipid peroxidation, and reduction in glutathione peroxidase 4 (GPX4) enzyme activity and levels. Aberrant liquid-liquid phase separation (LLPS) of tau drives the growth and maturation of NFTs contributing to AD pathogenesis.

Intrinsically Disordered Ku Protein-Derived Cell-Penetrating Peptides.

Efficient delivery of bioactive ingredients into cells is a major challenge. Cell-penetrating peptides (CPPs) have emerged as promising vehicles for this purpose. We have developed novel CPPs derived from the flexible and disordered tail extensions of DNA-binding Ku proteins.

Glucose-Responsive Self-Regulated Injectable Silk Fibroin Hydrogel for Controlled Insulin Delivery.

Stimuli-responsive drug delivery systems are gaining importance in personalized medicine to deliver therapeutic doses in response to disease-specific stimulation. Pancreas-mimicking glucose-responsive insulin delivery systems offer improved therapeutic outcomes in the treatment of type 1 and advanced stage of type 2 diabetic conditions. Herein, we present a glucose-responsive smart hydrogel platform based on phenylboronic acid-functionalized natural silk fibroin protein for regulated insulin delivery.

A natural polyphenol activates and enhances GPX4 to mitigate amyloid-β induced ferroptosis in Alzheimer's disease.

Ferroptosis, an iron-dependent cell death, plays a crucial role in the pathology of Alzheimer's disease (AD). Several characteristics of AD, including excessive iron accumulation, elevated lipid peroxide and reactive oxygen species (ROS) levels, and decreased glutathione peroxidase 4 (GPX4) levels, align with the features of ferroptosis. While traditional methods of inhibiting ferroptosis have centered on chelating Fe and trapping radicals, therapeutic strategies that modulate the GPX4 axis to mitigate ferroptosis in AD are yet to be explored.

Multifunctional Architectures of Cyclic Dipeptide Copolymers and Composites, and Modulation of Multifaceted Amyloid-β Toxicity.

Alzheimer's disease (AD) is a major neurodegenerative disorder primarily characterized by the β-amyloid (Aβ42) misfolding and aggregation-associated multifaceted amyloid toxicity encompassing oxidative stress, neuronal death, and severe cognitive impairment. Modulation of Aβ42 aggregation various structurally anisotropic macromolecular systems is considered effective in protecting neuronal cells. In this regard, we have developed a cyclic dipeptide (CDP)-based copolymer (CP) and explored its material and biomedical properties.

Antiplasmodial and Antimalarial Activity of 3,5-Diarylidenetetrahydro-2H-pyran-4(3H)-ones via Inhibition of Plasmodium falciparum Pyridoxal Synthase.

A series of 22 different 3,5-diarylidenetetrahydro-2H-pyran-4(3H)-ones (DATPs) were synthesized, characterized, and screened for their in vitro antiplasmodial activities against chloroquine (CQ)-sensitive Pf3D7, CQ-resistant PfINDO, and artemisinin-resistant PfMRA-1240 strains of Plasmodium falciparum. DATP 19 (3,5-bis(4-hydroxy-3,5-dimethoxybenzylidene)tetrahydro-2H-pyran-4(3H)-one) was found to be the most potent (IC 1.07 μM) against PfMRA-1240, whereas 21 (3,5-bis(3,4,5-trimethoxybenzylidene)tetrahydro-2H-pyran-4(3H)-one) showed IC values of 1.

Dendrimer Architectonics to Treat Cancer and Neurodegenerative Diseases with Implications in Theranostics and Personalized Medicine.

Integration of diagnostic and therapeutic functions in a single platform namely theranostics has become a cornerstone for personalized medicine. Theranostics platform facilitates noninvasive detection and treatment while allowing the monitoring of disease progression and therapeutic efficacy in case of chronic conditions of cancer and Alzheimer's disease (AD). Theranostic tools function by themselves or with the aid of carrier, liposomes, micelles, polymers, or dendrimers.

Molecular Architectonics-guided Design of Biomaterials.

The quest for mastering the controlled engineering of dynamic molecular assemblies is the basis of molecular architectonics. The rational use of noncovalent interactions to programme the molecular assemblies allow the construction of diverse molecular and material architectures with novel functional properties and applications. Understanding and controlling the assembly of molecular systems are daunting tasks owing to the complex factors that govern at the molecular level.