Table 2.
Missing evidences or open questions about α-synuclein spreading in PD.
| Open questions |
|---|
| What is the composition and structure of recombinant α-syn seeds, brain homogenates samples or LB-purified samples? |
| What are the α-syn species responsible for toxicity and spreading in recombinant α-syn seeds, brain homogenates samples or LB-purified samples? |
| Are there differences in biophysical or structural properties between α-syn species responsible for toxicity and spreading? |
| Does spreading implies infectivity? |
| Are α-syn species specific from a synucleinopathy to another? Is there a strain notion? |
| Are cofactors (intracellular or extracellular) necessary for self-propagation? |
| What is the contribution of the axonal transport in the spreading process? |
| Is glia involved in propagation to interconnected brain structures? |
| Is there a common pathway/pattern for tissue migration? |
| What is the mechanism of cell death in those α-syn spreading based models? Does the immune response play a role? |
| How to improve the reproducibility of recombinant α-syn seeds? α-syn assembly by PMCA or qRT-QuIC might overcome this obstacle. |
| Can we extrapolate the results obtained in α-syn spreading based models into human diseases? |
| Does the other neurodegenerative-associated proteins (Aβ, tau, huntingtin …) share the same spreading-toxic properties of α-syn? |
α-syn, α-synuclein; Aß, amyloid-beta; LB, Lewy body; PMCA, protein misfolding cyclic amplification; qRT-QuIC, quantitative real-time quaking-induced conversion.