Prion-like Diseases

In recent years a growing number of scientific studies has demonstrated that there is a common role for prions in neurodegenerative pathology. Indeed, aggregated proteins identified in other neurodegenerative disorders, such as Alzheimer's disease (AD) and Parkinson's disease (PD), have also been shown to spread through neurons in a prion-like fashion. These findings open the new possibility for therapeutic treatments that target the misfolded protein aggregates and prevent cell-to-cell transmission.

The major component of aggregates present in Parkinson's disease patients is a-synuclein (α-syn), a small, soluble, phospholipid-binding protein concentrated in presynaptic terminals. α-syn, is a natively unfolded protein, which may undergo dramatic structural changes resulting in the formation of β-sheet rich assemblies, including oligomers and fibrils. Several data have shown that recombinant α-syn protein is able to assemble in vitro into aggregates with morphologies and characteristics similar to those extracted from PD-affected brains. Moreover, increasing evidence suggests that in vitro formed α-syn aggregates may be taken up and propagated between cells in a prion-like manner.

Recently, in our lab [1], we showed that recombinant human α-syn could acquire prion-like properties once it is converted into a defined b-sheet-rich structure. We are currently evaluating the mechanisms involved in α-syn fibril spreading and in endogenous protein aggregation to find new molecular targets for treating PD patients.

 


1. Aulic, S., et al., Defined alpha-synuclein prion-like molecular assemblies spreading in cell culture. BMC Neurosci, 2014. 15: p. 69.

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