Calling α-synuclein a prion is scientifically justifiable

Excerpt

For more than a decade, the “prion-like” hypothesis for Parkinson’s disease (PD) has remained one of the most controversial topics in neurodegenerative disease research [21, 34]. Seminal studies revealed that α-synuclein pathology in the brains of PD patients follows a stereotypical progression pattern and that α-synuclein aggregates can spread between cells [3, 9], leading to the theory that a cell-to-cell propagation of protein misfolding may drive disease progression in PD and related synucleinopathies such as dementia with Lewy bodies and multiple system atrophy (MSA). At the core of the prion-like hypothesis is the notion that self-propagating α-synuclein aggregates are able to escape from a cell, enter a neighboring cell, and then act as a seed to induce the aggregation of α-synuclein in the recipient cell. This non-cell autonomous mechanism is similar to what occurs in prion diseases such as Creutzfeldt-Jakob disease (CJD), where misfolded prion protein (PrP) catalyzes the conformational conversion of normal PrP into additional copies of the misfolded form (PrP^Sc). The ability of prions to self-propagate allows them to spread within host tissues and underlies the transmissible nature of the prion disorders [29]. Given the similarities between α-synuclein aggregates and prions, it is not surprising that there has been considerable debate over whether they should be referred to as “prions”, “prion-like”, or something else entirely [33]. …