Thanks for those links jeffreyn, very interesting.

I have "walked across minefields" often when thinking about protein (mis)folding with my colleagues and may do so again.

I think that the critical experiment to show whether misfolded proteins other than PrP have prion-like properties is to use a mouse knock-out model. For example, one could make (say) α-synuclein KOs and then challenge them with misfolded α-synuclein. The prediction is that not much will happen to the KOs but wild-type mice will get sick because of the infectious (prion-like) properties of misfolded α-synuclein. I don't know if this or similar has been done.

This experiment has been done with mouse PrP KOs - they did not respond to the challenge of misfolded PrP compared to WT mice, who became sick. I heard about this at a conference - the speaker, somewhat flippantly, summed it up with the last slide; "PrP KO mice are OK.".

This is personal for me. A much-loved uncle of mine in NZ died from PD a couple of years ago. My job, apart from offering family support, was to translate what his care team told him into English.

I think that it would be best if investigators of the various protein misfolding diseases focused on mechanisms without being unduly fussed about "angels on a pinhead" arguments about prions.