A laboratory study indicates that the main protein involved in Parkinson’s disease pathology does not behave as a prion when overexpressed.
In Parkinson’s disease, the protein alpha-synuclein aggregates within neurons of patients and appears to propagate across interconnected areas of the brain. How this happens remains largely unknown. It has been proposed that alpha-synuclein may behave like a prion: pathological forms of the protein may be capable of changing the conformation of normal alpha-synuclein and thus triggering its aggregation and neuron-to-neuron propagation (a phenomenon referred to as “seeding”). Recent findings by scientists reveal that aggregation, spreading and pathology caused by alpha-synuclein do not necessarily involve prion-like seeding. Instead, they could be triggered by enhanced alpha-synuclein expression and trans-neuronal passage of monomeric and oligomeric forms of the protein.
“We believe that these findings bear a number of important implications for disease pathogenesis. Not only can we conclude that long-distance diffusion of alpha-synuclein does not necessarily require the generation of prion-like species, » said researcher Donato Di Monte. « Our data also reveal that spreading and pathology can be triggered by simple overexpression of the protein and are mediated, at least initially, by monomeric and/or oligomeric alpha-synuclein.”
Researchers report on this in the journal Brain.