Supervisors info:
Τρουγκάκος Ιωάννης, Καθηγητής, Τμήμα Βιολογίας, Εθνικό και Καποδιστριακό Πανεπιστήμιο Αθηνών
Summary:
Proteostasis is a process that regulates the structure and the function of the proteins within the cells, with aim to maintain the integrity of the proteome and consequently, the health of the whole body. This is achieved through a complicated system that ensures the proteome's quality, known as proteostasis network. This network is responsible to fold, hold, or degrade a protein and consists of interdependent systems that recognize and rescue or degrade misfolded or non-functional polypeptides. The key components of the proteostasis network are the two main degradation machineries of the cell, i.e. the ubiquitin-proteasome and autophagy-lysosome pathways, the NRF2/KEAP1 signaling pathway, which mobilizes cellular responses to oxidative and/or electrophilic stress, and the molecular chaperones.
The deregulation of proteostasis leads to proteomic instability and is considered as one of the hallmarks of aging. During aging, the proteostasis network malfunctions reducing signaling and repair pathways and accumulating high levels of stressors associated with the cellular senescence and age-related diseases, such as cancer. Studies support that activating the signaling pathways of the proteostasis network can reduce the morbidity and increase the longevity of the organisms. Also, the correlation of the evolution of carcinogenesis with the mechanisms of the proteome quality control leads to new efforts to cancer treatment.
However, despite the complicated systems involved in aging, some mechanisms that have been found can increase life expectancy, such as calorie restriction. In recent years, natural products have been found that can delay the cellular senescence in human cells or the in vivo aging in model organisms activating the proteostasis network. Natural products are an extremely rich resources of bioactive compounds and indicate a field of biomedical research for possible pharmaceutical or cosmetic use.
Following an extensive screening in order to identify bioactive molecules against aging and cancer, in this thesis, we studied natural products, isolated from marine organisms and plants. More specifically, we examined their effect on ubiquitin-proteasome and autophagy-lysosome pathways, on the antioxidant response, on the regulation of the network of molecular chaperones and on the DNA damage repair, proving their beneficial effect in these mechanisms. However, further studies need to be conducted on these mechanisms in order to fully elucidate the way by which they can delay cellular senescence.
Keywords:
Proteostasis network, Aging, Cancer, Natural products
