engleski

The effect of ASS234 on tau phosphorylation in vitro

Alzheimer’s disease (AD) is the most common cause of dementia in the elderly (affecting over 30 million people worldwide). AD is characterized by the presence in the brain of plaques composed of amyloid beta peptide and of neurofibrillary tangles made of hyperphosphorylated protein tau. In AD, the balance of tau kinase and phosphatase activity is shifted, creating a highly phosphorylated species of tau. This raises the fraction of unbound tau, which is no longer attached to microtubules (MT), allowing for monomeric hyperphosphorylated tau to bind to one another to produce oligomers. Fusion of oligomers leads to the formation of paired helical filaments, the primary constituent of neurofibrillary tangles (NFT). A number of neuroprotective strategies are being suggested to counter tau hyperhosphorylation and to reduce tau aggregates: 1) MT-stabilizing agents, 2) modulation of tau phosphorylation, 3) tau aggregation inhibitors, 4) targeting extracellular tau oligomers, 5) targeting tau clearance, and 6) targeting tau proteolysis. A multipotent, blood-brain barrier-permeable compound ASS234, has already been shown to inhibit Aβ aggregation, possesses antioxidant properties, and protects from Aβ-induced apoptosis in vitro (Bolea et al., Curr. Alzheimer Res., 2013), but its properties in regard to tau phosphorylation and aggregation have not been yet studied. The goal of this study was to assess the influence of ASS234 on tau phosphorylation in SH-SY5Y cells. Preliminary results of the study will be presented and discussed during the poster session.

ASS234; SH-SY5Y cells; Alzheimer’s disease; tau phosphorylation

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