No abstract

Aging is a multifactorial process determined by molecular, cellular and systemic factors and it is well established that advancing age is a leading risk factor for several neurodegenerative diseases. In fact, the close association of aging and neurodegenerative disorders has placed aging as the greatest social and economic challenge of the 21st century, and age-related diseases have also become a key priority for countries worldwide. The growing need to better understand both aging and neurodegenerative processes has led to the development of simple eukaryotic models amenable for mechanistic studies. Saccharomyces cerevisiae has proven to be an unprecedented experimental model to study the fundamental aspects of aging and to decipher the intricacies of neurodegenerative disorders greatly because the molecular mechanisms underlying these processes are evolutionarily conserved from yeast to human. Moreover, yeast offers several methodological advantages allowing a rapid and relatively easy way of establishing gene-protein-function associations. Here we review different aging theories, common cellular pathways driving aging and neurodegenerative diseases and discuss the major contributions of yeast to the state-of-art knowledge in both research fields.

The low gene transfer efficiency of chitosan-DNA polyplexes is a consequence of their high stability and consequent slow DNA release. The incorporation of an anionic polymer is believed to loosen chitosan interactions with DNA and thus promote higher transfection efficiencies. In this work, several formulations of chitosan-DNA polyplexes incorporating hyaluronic acid were prepared and characterized for their gene transfection efficiency on both HEK293 and retinal pigment epithelial cells. The different polyplex formulations showed morphology, size, and charge compatible with a role in gene delivery. The incorporation of hyaluronic acid rendered the formulations less stable, as was the goal, but it did not affect the loading and protection of the DNA. Compared with chitosan alone, the transfection efficiency had a 4-fold improvement, which was attributed to the presence of hyaluronic acid. Overall, our hybrid chitosan-hyaluronic acid polyplexes showed a significant improvement of the efficiency of chitosan-based nonviral vectors in vitro, suggesting that this strategy can further improve the transfection efficiency of nonviral vectors.