Fatemeh Bahadori
Bezmialem Vakif University, Turkey
Title: Apolipoprotein E4 mediated targeting of blood brain barrier using nano-micellar metal chelators for treatment of Alzheimer’s disease
Biography
Biography: Fatemeh Bahadori
Abstract
Alzheimer’s Disease (AD) is one of the most important disorders of current century. Many pathological factors are contributed in the progress of this disease, the most important one being aggregation of Amyloid β (Aβ) in brain. Thus, prevention of Aβ aggregation could have an important role in the treatment of AD. It is well-defined that some divalent metals namely iron, copper and zinc play role in Aβ aggregation. Thus, formulations with metal-proteinattenuating (MPA) and metal chelating activity (metal chelators (MCs))could play a possible role as co-treatment agents for AD.However,MCs are generally neurotoxic and more importantly, they are hydrophilic which means they wouldn’t pass through Blood Brain Barrier (BBB). Since the structure-activity relationship of MCsis defined as carrying oxygen bearing functional groups in ortho position, we chose series of plants, which are rich in poly-phenolic compounds with this special property. We also chose a series of synthetic compounds with high MC activity. Plant extracts were prepared and screened for their MC and MPA activity by incubating with Aβ aggregates. The methanolic extract of Rosmarinusofficinalis(RO) showed the highest metal chelating and metal protein attenuating activity while PyrrolidineDithiocarbamate (PDTC) was the most active and non-toxic synthetic material. Nano-micellar Poly Lactic-co-Glycolic Acid (PLGA) formulation of RO and PDTC was prepared and surface modified with Apolipoprotein E4. Both formulations showed satisfying MPA and MC activity with a hydrodynamic size less than 200 nm, while, Apo E4 provided targeting property using its specialized receptors on BBB.