Mechanisms of spermidine mediated neuroprotection

Aging is accompanied by cellular and/or organismal deterioration, causing multiple diseases and ultimately resulting in death. In our aging society neurodegenerative diseases, such as the two most common pathologies, Parkinsons (PD) - and Alzheimers disease (AD) are prevalent and will become even more important within the next decades. The constant rise of incidence of, in particular, age-associated neurodegeneration among our population demands a better understanding of the underlying mechanisms to be able to propose new ameliorating interventions. But it is impossible to track the etiology of the disorders direct on AD and PD patients. Therefore, suitable model organisms are needed to reveal the causative players of disease onset and progression. Within the last decade, the fruit fly Drosophila melanogaster has become a well-established model organism to study human development and diseases, mainly due to the widely investigated anatomy and the broad spectrum of applicable genetic and molecular techniques, including methods to study synaptic activity as well as behavior or motor function, learning and memory. On the other hand, mouse AD and PD models, being less easy to modify genetically, but standing evolutionary much closer to human, are a perfect complementation of the fly models for validation purposes. Fly and mouse AD and PD models develop phenotypical symptoms characteristic for these pathologies (e.g. degradation of motoric and cognitive functions). Novel strategies for the treatment of both Alzheimers disease and Parkinsons disease are desperately needed, since a cure for both AD and PD has not been found yet. Pathological aggregation and wrong folding of proteins is underlying both AD and PD, therefore promotion of protein clearance (e.g. by autophagy) could be a promising new concept. Recently, our group reported that external application of spermidine, a naturally occurring polyamine, induces autophagy and increases the length of life in a variety of phyla. Further, we have promising results pointing a neuroprotective function of spermidine. Herein, we propose a systematic and exhaustive analysis of spermidine mediated neuroprotection in fly and mouse models of AD and PD.