Proteasomes are constituents of the cellular proteolytic networks that maintain protein homeostasis through regulated proteolysis of normal and abnormal (in any way) proteins. Proteasome activation in cell lines has been shown to result to cellular lifespan extension and to exert protein anti-aggregation activity.
Using Caenorhabditis elegans as a model, we analyzed in detail the proteasome status upon the progression of ageing and Alzheimer's disease (AD) and we investigated the effects of enhanced proteasome activities on the progression of the above mentioned phenomena. The obtained results were validated in human and murine cells of neuronal origin. More specifically, proteasome activation in C. elegans either through genetic means or through compounds resulted in enhanced levels of proteasome activities that led to a SKN-1- and proteasome activation-dependent lifespan extension. The elevated proteasome function conferred lower paralysis rates in various AD nematode models accompanied by decreased Aβ deposits thus ultimately decelerating the progression of AD phenotype. More importantly, similar positive results were also delivered in human neuroblastoma cells and in murine cortical neurons.
Based on these results we have searched for natural and synthetic compounds with proteasome activating properties and we have found lead compounds that are currently under detailed investigation. Preliminary results revealed their beneficial effects against ageing. In total, our results suggest that proteasome activation with downstream positive outcomes on ageing and AD, an aggregation-related disease, is feasible in both a genetic and a non-genetic manipulation manner in cells as well as in a multicellular organism. Moreover they unveil the need for identification of anti-ageing and anti-amyloidogenic compounds either through chemical synthesis or among the nutrients found in our normal diet.
18 Aprile
The seminar will be held by Prof. Niki Chondrogianni
of the Institute of Biology, Medicinal Chemistry and Biotechnology National Hellenic Research Foundation, Athens, in room C (building CU010) at 12:00.