Paper BI-WeA3
Curcumin Offers Neuroprotection by Inhibiting amyloid-β Insertion into Membranes

Wednesday, October 20, 2010, 2:40 pm, Room Taos

Alzheimer’s disease (AD) is a major cause of dementia in elderly people, affecting 5 million people in USA alone. AD is caused by the abnormal accumulation of aggregated amyloid beta peptides (39 to 43 amino acid residues) in the brain. Amyloid beta peptides are proteolytic products of the amyloid precursor protein of unknown function. Unfortunately, there are no cures available for this disease. However, there are several mechanisms purposed to cause and cure AD. The lipid membrane has been shown to mediate the fibrillogenesis and toxicity of Alzheimer's disease amyloid beta (Aβ) peptide. Several reports have linked the insertion of Aβ peptide into membranes as a possible mechanism of neurotoxicity. We hypothesized that small molecules capable of preventing the insertion of Aβ into membranes may ameroliate Aβ toxicity. Therefore, we investigated the effect of curcumin, a naturally occurring anti-inflammatory and antioxidant compound that suppresses oxidative damage, inflammation, cognitive deficits, and amyloid accumulation, on Aβ40 induced toxicity and in Aβ40 insertion into 1,2-dimyristoyl-sn-glycero-3-phosphoglycerol (DMPG) monolayer using surface pressure insertion isotherms and fluorescence microscopic techniques. We found that curcumin attenuates Aβ40 induced neuronal toxicity by inhibiting the insertion of Aβ into membranes possibly by interacting with membranes. Our data also demonstrated that neuroprotective action of curcumin in Aβ induced toxicity does not exclusively come through oligomerization inhibition, indicating that c urcumin-membrane interaction but not curcumin-Aβ is associated in curcumin mediated neuroprotection. Altogether, our study suggests that curcumin-like small molecules inhibitors of Aβ insertions into membranes could be potential target to cure AD.