Studies on therapeutic potential of synthetic as well as herbal compounds for Alzheimer s disease using transgenic Drosophila model

Abstract

Alzheimer s disease (AD) is a neurodegenerative disease that involves the aggregation and deposition of the mainly two polypeptides and#946;-amyloid (Aand#946;42) and Tau. The former is the result of processing of APP by and#946; and and#947;-secretases while later one form neurofibrillary tangles (NFTs) which consist of paired helical filaments of hyper phosphorylated tau protein. To date, it remains unclear about the etiology of the disease and no cure is available. Therefore people are continuously working to find out a suitable therapeutic target for the treatment of AD. Multiple lines of evidence supports that overproduction of Aand#946;42 through APP processing results in a neurodegenerative cascade leading to self-aggregation, synaptic dysfunction, formation of intra-neuronal fibrillary tangles and gradual neuron loss in hippocampus area of the brain. Basically, there are two main toxic species, Aand#946;40 and Aand#946;42, with Aand#946;42 being more hydrophobic in nature and more prone to self- aggregation which results into Aand#946; fibril formation. Since Aand#946; aggregation is hypothesized to be the most crucial step of the pathogenic process of AD, the strategy to inhibit Aand#946;42 aggregation has emerged as one of the promising approaches to treat AD. In the current scenario, major focus involves deciphering the role of numerous synthetic as well as herbal compounds as inhibitors of Aand#946; aggregation.