Nanotechnology for tau pathology in Alzheimer's disease.

Tau protein aggregation is a defining characteristic of Alzheimer's disease (AD), leading to the formation of neurofibrillary tangles that disrupt neural communication and ultimately result in cognitive decline. Nanotechnology presents novel strategies for both diagnosing and treating Alzheimer's disease. Nanotechnology. It has become a revolutionary tool in the fight against Alzheimer's disease, particularly in addressing the pathological accumulation of tau protein. This review explores the relationship between tau-related neurophysiology and the utilization of nanotechnology for AD treatment, focusing on the application of nanomaterials to regulate tau phosphorylation, hinder tau aggregation and propagation, stabilize microtubules, eliminate pathological tau and emphasize the potential of nanotechnology in developing personalized therapies and monitoring treatment responses in AD patients. This review combines tau-related neurophysiology with nanotechnology to provide new insights for further understanding and treating Alzheimer's disease.

Designing nanodiscs as versatile platforms for on-demand therapy.

Nowadays, there has been an increasing utilization of nanomedicines for disease treatment. Nanodiscs (NDs) have emerged as a novel platform technology that garners significant attention in biomedical research and drug discovery. NDs are nanoscale phospholipid bilayer discs capable of incorporating membrane proteins and lipids within a native-like environment. They are assembled using amphiphilic biomacromolecular materials, such as apolipoprotein A1 or membrane scaffold proteins (MSPs), peptides, and styrene-maleic acid polymers (SMAs). NDs possess well-defined sizes and shapes, offering a stable, homogeneous, and biologically relevant environment for studying membrane proteins and lipids. Their unique properties have made them highly desirable for diverse applications, including cancer immunotherapy, vaccine development, antibacterial and antiviral therapy, and treating Alzheimer's disease (AD) and diabetes-related conditions. This review discusses the classifications, advantages, and applications of NDs in disease therapy.

Design, synthesis, and biological evaluation of tetrahydroisoquinolines derivatives as novel, selective PDE4 inhibitors for antipsoriasis treatment.

Psoriasis is a kind of chronic inflammatory skin disorder, while the long-term use of conventional therapies for this disease are limited by severe adverse effects. Novel small molecules associated with new therapeutic mechanisms are greatly needed. It is known that phosphodiesterase 4 (PDE4) plays a central role in regulating inflammatory responses through hydrolyzing intracellular cyclic adenosine monophosphate (cAMP), making PDE4 to be an important target for the treatment of inflammatory diseases (e.g. psoriasis). In our previous work, we identified a series of novel PDE4 inhibitors with a tetrahydroisoquinoline scaffold through structure-based drug design, among which compound 1 showed moderate inhibition activity against PDE4. In this study, a series of novel tetrahydroisoquinoline derivatives were developed based on the crystal structure of PDE4D in complex with compound 1. Anti-inflammatory effects of these compounds were evaluated, and compound 36, with high safety, permeability and selectivity, exhibited significant inhibitory potency against the enzymatic activity of PDE4D and the TNF-α release from the LPS-stimulated RAW 264.7 and hPBMCs. Moreover, an in vivo study demonstrated that a topical administration of 36 achieved more significant efficacy than calcipotriol to improve the features of psoriasis-like skin inflammation. Overall, our study provides a basis for further development of tetrahydroisoquinoline-based PDE4 inhibitors against psoriasis.