A/Prof Anthony Tsarbopolous,
Department of Pharmacology,
University of Athens Medical School,
Date: Thursday, 22 October, 2015
Time: 11:00am – 12:00pm
Chairperson: A/Prof Gavin Dawe
Disease Modification Strategies for Alzheimer’s Disease: Hunting for Potential Inhibitors through Nature’s Arsenal
Neurodegenerative disorders such as Alzheimer’s Disease (AD) and Parkinson’s Disease are persistent progressive diseases and have a major health impact along with direct and indirect medical care costs. They are associated with abnormal accumulation and aggregation of disease-specific proteins and peptides and inclusion bodies in selected brain regions. In case of AD, it has been proposed that the beta amyloid peptide (Aβ) in the Aβ1-40 and Aβ1-42 forms, abnormal tau protein or probably both play critical role in the development of the disease. Understanding the aggregation mechanism and how to inhibit aggregate formation is therefore crucial and will have a major impact on health along with economical ramifications worldwide. In light of the suggested link between oxidative stress and neurodegeneration, it is proposed that endogenous antioxidants or dietary derived compounds may be prime candidates for anti-aggregation compounds preventing aggregation of Aβ and/or promoting clearance of Aβ aggregates.
In this presentation, we will demonstrate an integrated approach towards the evaluation of the antiamyloidogenic activity of isolated components isolated from endemic plants of Greece as putative aggregation inhibitors for the prevention of AD. Oleuropein (OE) isolated from olive leaves of Olea europaea, and several components from Crocus sativus L., which is cultivated in the Mediterranean region and South Asia for its red stigmas (saffron), have been characterized and screened for forming non-covalent complexes with the Aβ peptide. These Crocus sativus L.-derived bioactive constituents are trans- and cis-crocin-4 (TC-4 and CC-4) and crocin-3 (TC-3), trans-crocin-2 (TC-2), and other crocetin mono- and bis-ester glycoside compounds. The screening of these compounds was carried out by nano-electrospray ionization (ESI) MS, where the formation of 1:1 noncovalent complexes of Aβ with OE, TC-2, TC-3 and TC-4 was observed. Finally, in vitro screening was supplemented with cell viability assays using differentiated neuronal SH-SY5Y cells. At the cellular level, trans-crocetin and TC-4 did not appear to have any toxic effects at concentrations up to 10μM at both 24 and 72 hours. Moreover, trans-crocetin and TC-4 appear to modestly enhance cell proliferation at 24 hours of incubation with concentrations between 0.1 and 10 μM. This screening of natural products in terms of their antiamyloidogenic activity will provide insights into novel agents that could be prime candidates for anti-aggregation compounds, which could be eventually employed towards stabilizing the progress of AD.