Abstract

Alpha-synuclein (aS) is a disordered membrane binding protein that plays a key role in the development of Parkinson’s disease (PD). In PD aS self-assembles into filamentous structures called amyloid fibrils. These fibrils are chemically and mechanically very stable. Once formed they cluster into characteristic cellular inclusions such as Lewy bodies. The forces driving inclusion body formation and their role in the disease pathology remain elusive. Lewy body formation has been associated with both neuroprotection and toxicity. In this talk, I will summarize our recent work on the accumulation aS in functionally different inclusions in cells and on the forces driving self-assembly of aS fibrils in supra-fibrillar structures in vitro. I will discuss how we used a broad repertoire of biophysical techniques to characterize aS amyloid micro- and nano-structures and obtain insight into possible disease mechanisms.