The aggregation of α-synuclein (αS), a neuronal protein that is abundant at the pre-synaptic terminals, is associated with a range of highly debilitating neurodegenerative conditions including Parkinson’s Disease (PD). Fibrillar aggregates of αS are the major constituents of proteinacious inclusions known as Lewy bodies that form in dopaminergic neurons of patients suffering from these conditions. The function of αS, however, is currently unknown, with evidences suggesting a role in the regulation of the trafficking of synaptic vesicles.
We study the structure and interactions of αS in its functional state and in the form of pathological aggregates by means of biophysics and biomolecular NMR [1]. Our research has identified the nature of the physiological membrane interaction of αS and elucidated how this transient binding is involved functional processes such as the clustering of synaptic vesicles [2] or their docking onto the plasma membrane [3]. In the context of αS aggregation, we focus on the properties of elusive intermediate oligomers and how they impair neuronal function in the context of PD [4-5].
References
1. Fusco G, et al, (2014) Nat Commun 5:3827.
2. Man WK, et al, (2021) Nat Commun 12:927.
3. Fusco G, et al, (2016) Nat Commun 7:12563.
4. Fusco G, et al, (2017) Science 358:1440-3.
5. Cascella, et al, (2019) ACS chem bio 14:1352-1362.
18/03/2022 Alfonso De Simone Department of Pharmacy, University of Naples Federico II