Drug Development.

Background: Several studies have shown the influential role of nutraceuticals on cognition and mental functions. Dihydroxytrimethoxyflavone, a natural flavone found in herbal drugs, is documented to be neuroprotective in different model systems. Nevertheless, possible memory improvement effects of dihydroxytrimethoxyflavone via nuclear factor-E2-related factor 2 (Nrf2) (a crucial regulator of antioxidative system) has not been systematically evaluated.

Drug Development.

Background: Traditionally associated with recreational and spiritual uses, psychedelics have gained attention in psychotherapy for their therapeutic potential. Functioning as potent 5-hydroxytryptamine (5HT) agonists, these compounds have demonstrated the ability to enhance neural plasticity by activating serotoninergic and glutamatergic systems. Despite these recognized effects, their role in treating neurodegenerative disorders, particularly dementia, remains relatively unexplored.

Drug Development.

Background: TAR-DNA-binding protein 43 (TDP43), is a pathologic marker in neurodegenerative diseases including frontotemporal lobar degeneration and amyotrophic lateral sclerosis. The aggregation of TDP-43, a crucial RNA-binding protein, is a consequence of post-translational modifications (PTMs) that disrupt its normal function. PTMs such as phosphorylation and ubiquitination contribute to the aberrant accumulation of TDP-43 aggregates, leading to neurodegenerative disorders like amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD).

Drug Development.

Background: The increased incidence of Alzheimer's disease (AD) rate represent an unmet medical need and thus critical for the development of novel molecular therapeutics. Recent work focusing on patients with apoE4 alleles has highlighted the association of brain cholesterol dysregulation with elevated pathological burden and neurodegeneration. These studies have highlighted the importance of the nuclear receptor Liver X receptor (LXR) for developing AD therapies.

Drug Development.

Background: Neurological disorders are at epidemic levels in the world today. Various proteins are being targeted for the development of novel molecular therapeutics; however, no small-molecule inhibitors have been discovered. Recent studies suggest that there are few molecules in clinical trials for various secretase (α, β, and γ), caspase, and calpain inhibitors.