0000000000405937
AUTHOR
Rakez Kayed
showing 6 related works from this author
NOVEL SMALL MOLECULES THAT BIND AND/OR MODULATE DIFFERENT FORMS OF TAU OLIGOMERS
2020
The present invention relates to novel small molecules of Formulas I, II, III, IIIa, IIIb, and IV and pharmaceutically acceptable salts thereof, as well as the preparation and the use thereof.
Azure C Targets and Modulates Toxic Tau Oligomers.
2018
Alzheimer's disease (AD) is the most common age-related neurodegenerative disorder affecting millions of people worldwide. Therefore, finding effective interventions and therapies is extremely important. AD is one of over 20 different disorders known as tauopathies, characterized by the pathological aggregation and accumulation of tau, a microtubule-associated protein. Tau aggregates are heterogeneous and can be divided into two major groups: large metastable fibrils, including neurofibrillary tangles, and oligomers. The smaller, soluble and dynamic tau oligomers have been shown to be more toxic with more proficient seeding properties for the propagation of tau pathology as compared to the …
Modulating disease-relevant tau oligomeric strains by small molecules
2020
The pathological aggregation of tau plays an important role in Alzheimer's disease and many other related neurodegenerative diseases, collectively referred to as tauopathies. Recent evidence has demonstrated that tau oligomers, small and soluble prefibrillar aggregates, are highly toxic due to their strong ability to seed tau misfolding and propagate the pathology seen across different neurodegenerative diseases. We previously showed that novel curcumin derivatives affect preformed tau oligomer aggregation pathways by promoting the formation of more aggregated and nontoxic tau aggregates. To further investigate their therapeutic potential, we have extended our studies o disease-relevant bra…
Binding and neurotoxicity mitigation of toxic tau oligomers by synthetic heparin like oligosaccharides.
2018
Well-defined heparin like oligosaccharides up to decasaccharides were synthesized. It was discovered for the first time that heparin oligosaccharides, as short as tetrasaccharides, can bind with the most toxic tau species, i.e., tau oligomers with nM KD. The binding significantly reduced the cellular uptake of toxic tau oligomers and protected the cells from tau oligomer induced cytotoxicity.
Toxic Tau Oligomers Modulated by Novel Curcumin Derivatives
2019
AbstractThe pathological aggregation and accumulation of tau, a microtubule-associated protein, is a common feature amongst more than 18 different neurodegenerative diseases that are collectively known as tauopathies. Recently, it has been demonstrated that the soluble and hydrophobic tau oligomers are highly toxic in vitro due to their capacity towards seeding tau misfolding, thereby propagating the tau pathology seen across different neurodegenerative diseases. Modulating the aggregation state of tau oligomers through the use of small molecules could be a useful therapeutic strategy to target their toxicity, regardless of other factors involved in their formation. In this study, we screen…
Curcumin as Scaffold for Drug Discovery against Neurodegenerative Diseases
2021
Neurodegenerative diseases (NDs) are one of major public health problems and their impact is continuously growing. Curcumin has been proposed for the treatment of several of these pathologies, such as Alzheimer’s disease (AD) and Parkinson’s disease (PD) due to the ability of this molecule to reduce inflammation and aggregation of involved proteins. Nevertheless, the poor metabolic stability and bioavailability of curcumin reduce the possibilities of its practical use. For these reasons, many curcumin derivatives were synthetized in order to overcome some limitations. In this review will be highlighted recent results on modification of curcumin scaffold in the search of new effective therap…