Study of Potential Drug for Alzheimer’s Disease: Small Organic Molecules, 1,5-DHN and TMPyP Inhibit Amyloid-β peptide Aggregation and Quench Hydroxyl Radicals

Alzheimer disease (AD) is recognized as the six leading cause of the death in the United States. As of now, there is no cure for this fatal disease. The current treatment methods can only temporarily slow the worsening of symptoms. Research data suggested that an excess generation of hydroxyl radical in the brain causing the aggregation of Amyloid-β (Aβ) peptide which is considered to be responsible for Alzheimer's disease. Thus, there is a pressing need to find a suitable drug which can quench hydroxyl radicals effectively and stop or slow down the formation of aggregation of Aβ peptide. The primary objective of the project is to find out a dual functional drug which can quench the reactive hydroxyl radicals produced in the brain and prevent Aβ peptide chains to come close to form Aβ peptide aggregate at the same time. A small organic molecule 1,5-dihydroxynapthalene (DHN) was found to quench hydroxyl radical at a rate of 3 X 10-4s-1. An independent experiment suggested that it intercalated efficiently into the Aβ peptide chains. Upon addition of meso-tetra(N-methyl-4-pyridyl)porphyrin tetrachloride (TMPyP) with DHN, a strong synergistic effect in quenching the hydroxyl radical and intercalating into the Aβ peptide chains was observed. This data suggests that DHN or DHN & TMPyP are the potential drug for Alzheimer disease treatment.