Catching elusive molecular interactions behind Parkinson’s Disease

ABSTRACT

Neurodegenerative conditions associated with protein aggregation are becoming increasingly prevalent in western societies, affecting more than 11 million people in Europe. PD is the second most common neurodegenerative disorder with 10 million patients worldwide, resulting in a devastating social and economical burden. PD patients develop intracellular deposits, Lewy Bodies, in dopaminergic neurons. These inclusions are primarily formed of fibrillar aggregates of α-synuclein (αS), a disordered protein that localizes primarily in the synaptic termini. The function of αS is currently unknown, with evidence suggesting a role in the regulation of neurotransmitter release.

We have established a research programme based on molecular structural biology and cellular biophysics to reveal the transient interactions that govern the biological properties of αS in functional and pathological contexts. A major focus of our research is the binding with synaptic membranes, which is a key step in most of the biological processes involving αS. Our studies enabled to characterize fundamental mechanisms of functional relevance for αS [1-3] as well as the properties that enable its pathological aggregates to generate toxicity in neuronal cells and in animal models of PD [4,5].