UNIVERSITY OF MALTA LIFE SCIENCE RESEARCH SEMINARS Web: http://events.um.edu.mt/scisem/ Email: scisem@um.edu.mt Abstract form Title: Identification of natural polyphenols acting as inhibitors of amyloid beta-derived cellular damage Presenter: Rachel Cremona Contact address: Tel: (+356) 79860226 Fax: Email: rachel@icpconcepts.com Presentation date: 14th December 2009 Abstract Alzheimer’s disease is an incurable, degenerative and terminal disease that is generally prevalent in the elderly population. Research has provided evidence for a common mechanism of neurodegeneration whereby misfolding, aggregation and accumulation of otherwise normal proteins occurs in the brain. The proteins involved and the location of accumulation produce the varying clinical features for each of the neurodegenerative diseases. For this study the protein selected is the amyloidβ which is one of the three pathological signatures of Alzheimer’s Disease. One of the proposed mechanisms for Aβ neurotoxicity is membrane disruption and depolarization by permeabilization of the membrane, resulting in a change of ion homeostasis and deregulation of cellular signal transduction, leading to cell death. This research study forms part of a large-scale project. The main deliverables being: • • • • • • Establish a cell culturing protocol for SH-SY5Y Cytotoxicity screening of polyphenols and plant extracts on SH-SY5Y Identification of the most consistently potent compounds by comparing cytotoxicity results with those obtained from liposome permeabilization assay. Establish and optimize the cytotoxic assay to obtain required toxicity of pre-aggregated peptides Identify the minimum concentration of amyloid-β to induce this cytotoxicity on the neuroblastoma cell line. Application of the selected polyphenols/extracts and amyloid-β using varying combination sequences to determine protective, inhibiting/arresting or reversing function of the plant compounds. Considering the increased prevalence rate of such diseases, especially in the growing aging population, research into possible therapy would have major medical, social and economic implications.