1. Academic Validation
  2. Azure C Targets and Modulates Toxic Tau Oligomers

Azure C Targets and Modulates Toxic Tau Oligomers

  • ACS Chem Neurosci. 2018 Jun 20;9(6):1317-1326. doi: 10.1021/acschemneuro.7b00501.
Filippa Lo Cascio 1 2 3 Rakez Kayed 1 2
Affiliations

Affiliations

  • 1 Mitchell Center for Neurodegenerative Diseases , University of Texas Medical Branch , Galveston , Texas 77555 , United States.
  • 2 Departments of Neurology, Neuroscience and Cell Biology , University of Texas Medical Branch , Galveston , Texas 77555 , United States.
  • 3 Department of Experimental Biomedicine and Clinical Neuroscience , University of Palermo , 90127 Palermo , Italy.
Abstract

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 fibrillar Paired Helical Filaments (PHFs). Therefore, developing small molecules that target and interact with toxic tau oligomers can be beneficial to modulate their aggregation pathways and toxicity, preventing progression of the pathology. In this study, we show that Azure C (AC) is capable of modulating tau oligomer aggregation pathways at micromolar concentrations and rescues tau oligomers-induced toxicity in Cell Culture. We used both biochemical and biophysical in vitro techniques to characterize preformed tau oligomers in the presence and absence of AC. Interestingly, AC prevents toxicity not by disassembling the oligomers but rather by converting them into clusters of aggregates with nontoxic conformation.

Keywords

Tau oligomers; small molecules; tau aggregation; toxicity.

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