Marine natural products as aβ modulators

We have developed a drug discovery program in order to look for neuroprotective compounds from marine origin, showing biological activities relevant for preventing and/or treating neurodegenerative diseases. Thus, we have identified a family of marine compounds showing potent neuroprotective activity in several cellular models of oxidative stress. These molecules are also able to significantly reduce beta-amyloid (A beta) secretion in APP-transfected cell lines. This effect correlates with an increase of soluble APP (sAPP) and alpha APP (alpha APP) fragments, indicating that activation of the a-secretase pathway is involved. Additional experiments seem to suggest that these compounds could activate metalloproteases which are implicated in the A beta degradation. An active medicinal chemistry program has been developed, leading to several naturally-derived synthetic lead compounds with improved potency and ADME properties.