Abstract Body

The aggregation of alpha-synuclein (ASYN) in Lewy bodies and Lewy neurites is the typical pathological hallmark of Parkinson’s disease (PD) and other synucleinopathies. Mutations and multiplications in the gene encoding for ASYN are associated with familial and sporadic forms of PD, suggesting this protein plays a central role in the disease. However, the precise contribution of ASYN to neuronal dysfunction and death is still unclear. There is intense debate on the nature of the toxic species of ASYN, and little is still known about the molecular determinants of oligomerization and aggregation of ASYN in the cell.

By harnessing the power of various model organisms, we are making progress towards the understanding of the basic molecular mechanisms underlying PD and other synucleinopathies. In particular, we are ofusing on the effects of different posttranslational modifications (PTMs) on the toxicity and aggregation of ASYN.

Glycation, an age-associated PTM that is also increased in diabetes, is emerging as an important modification that affects ASYN aggregation and toxicity. In our recent work, we are investigating how different sugars affect the aggregation of ASYN, and how quality control mechanisms respond to the accumulation of glycated ASYN.

In conclusion, our data sheds new light into the molecular underpinnings of synucleinopathies, opening novel perspectives for therapeutic intervention.