Extracellular EDPs at high concentrations participate in neuronal cytoskeleton assembly and AD etiology

Abstract

Elastin in the Extracellular Matrix provides tissues with flexibility and degrades over time to release biologically active Elastin-Derived Peptides (EDPs). EDPs have recently been discovered to potentially mediate pathological conditions of Alzheimers Disease (AD). However, few studies have shown the regulation of EDPs on the neuronal function during ADprogression. Firstly, a meta-analysis on 11 related studies was conducted to pre-verify the hypothesis and to reduce experimental bias. After that, experiments on a mouse hippocampal cell-line (HT22) were set to test for both cell vitality and morphology after exposure to EDPs at different concentrations (0.0001 M-50 M) and durations (0-48 h). Cell vitality was assessed quantitatively using a cell counting kit and cell morphology assessed qualitatively using phalloidin staining on actin filaments. A rescue experiment was also set to discover potential ways of mitigating the effects of EDPs on cytoskeleton assembly. Data here showed statistically significant effects of EDPs on impacting cell vitality negatively at higher concentrations (>0.1 M) and longer durations (48 h). Cell morphology after EDPs incubation was also impacted with less F-actin stress fibers, which are essential for effective neuronal transmissions. Lastly, rescue experiments using galactose was found to considerably reduce the effects of EDPs on cell morphology. It was concluded that EDPs does negatively impact cell vitality and morphology of neurons. Given the cytoskeleton structures and assembly are important for neuronal function, the data indicated a pathological role of EDPs on the progression of AD.