Leonidas Stefanis is Professor of Neurology and Neurobiology at the Medical School of the University of Athens, Director of the Second Department of Neurology at “Attikon” Hospital, and collaborating investigator at the Foundation of Biomedical Research of the Academy of Athens (BRFAA), where he leads a research group working on Neurodegenerative Diseases. More specifically, his research involves the genetic basis of Parkinson’s Disease and related disorders, the mechanisms of neurotoxicity evoked by aberrant alpha-synuclein, as well as the pathogenic effects of genetic alterations in other genes linked to Parkinson’s Disease. Hehasco-authoredmorethan 100 publications in high-impact journals, he has received funding from various national and international funding sources, and he has served as member of the Editorial Board of important journals in the area of Neurobiology, as well as of committees of evaluation of research proposals, such as the European Research Council.
Genetic, neuropathological and biochemical data suggest that alpha-synuclein aggregation lies at the core of Parkinson’s Disease pathogenesis. Regulation of alpha-synuclein levels through protein degradation systems is a critical determinant of its neurotoxic potential. Furthermore, alpha-synuclein may aberrantly impact the protein degradation systems through which it is cleared, thus generating a positive feed-forward amplification loop leading to the disease. We will develop this concept, concentrating more on the lysosomal degradation pathway of Chaperone-Mediated Autophagy (CMA), and its reciprocal relationship to alpha-synuclein. We will focus in particular on the therapeutic potential of CMA enhancement as a therapeutic approach in synucleinopathies.