Search results for "Tau aggregation"

Small Molecules Targeting and Modulating Toxic Tau Oligomeric Strains

Alzheimer’s disease (AD) is one of over 18 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 neurofibrillary tangles (NFTs) and oligomers. Recently, it has been shown that tau oligomers are highly toxic in vitro and efficient seeds for the propagation of pathology as compared to NFTs. While the toxicity of recombinant tau oligomers has been studied extensively, within the same aggregation state, tau exhibits conformational differences, termed tau oligomeric strains. Due to the dynamic nature of these stra…

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…