Effect of Curcumin on aβ-42 Interaction with and Disruption of Lipid Membrane

Effect of Curcumin on Aβ-42 Interaction with and Disruption of Lipid Membrane

Alzheimer’s disease is a progressive, degenerative disorder
most common in individuals 65 and older, affecting approximately 48 million
individuals as of 2015. With a life expectancy of 3-9 years post-diagnosis and
the high cost of caring for these individuals, viable treatments and prevention
medications are necessary.

The main pathological hallmark of AD is the presence of
extracellular senile plaques made of amyloid beta (Aβ) protein. Two forms of Aβ
are found in AD: Aβ-40 the most abundant, Aβ-42 the most toxic. The
toxicity of Aβ protein is related to its capability to bind to the cell
membrane which leads to the production of pores and cell death. 

The Chi lab is investigating the protection of lipid
membranes via the use of curcumin. In this study, the neuroprotective mechanism
of curcumin on the highly toxic Aβ-42 protein was investigated by
using a combination of technics: Langmuir Blodgett trough, TEM and fluorescence.
First, the capability of curcumin to protect the lipid monolayer against
different aggregation forms of Aβ-42 was tested. We showed that
the insertion of Aβ-42 into the membrane was reduced in presence of
curcumin. Secondly, the effect of curcumin on Aβ-42 aggregation was
evaluated. Curcumin didn’t stop the aggregation of Aβ-42, but rather modified
the morphology of the fibrils which were more granular. Finally, the surface
activity of Aβ-42 co-incubated with curcumin was characterized by
an increase of the lag phase.

This study facilitated a better understanding of the
molecular mechanism of curcumin’s neuroprotective effect, which could
contribute to the development of treatments for AD.