So the idea that neurodegeneration is essential a manifestation of protein-specific prion disease is not a new idea[1][2][3][4][5] but is one which is steadily gaining traction. That said, from a complexity perspective we&#x27;re still at the tip of the iceberg.<p>There&#x27;s extensive evidence to suggest that the big, fiber-like aggregates that form in these diseases may in fact be neuroprotective, and represent a largely inert thermodynamic end state (basically a big inert crystal which kind of hangs out but doesn&#x27;t do much damage). More labile, smaller aggregates (basically blobs of protein stuck together) which are formed during the fibril formation process may in fact be more toxic, though again it really depends on who you ask.<p>How the toxicity is manifest is also totally unclear - is this a loss of function (proteins which aggregate disappear, so they can no longer do their job), gain of function (proteins which aggregate now interact with other things, leading to some new and bad outcomes) or somewhere in between? How does the cellular quality control system interface with all this? Why are certain cell types much more susceptible than others? How does the disease spread in the brain?<p>There are a lot of very smart people doing some amazing work. If you&#x27;re interested, off the top of my head I&#x27;d take a look at work by Sue Lindquist, Simon Alberti, Marc Diamond, Don Cleveland, Virginia Lee, Eric Ross, Paul Taylor, Rick Morimoto and David Eisenberg (just to get you started!).<p>The one thing I would say is that I wouldn&#x27;t treat this as cause for concern for interpersonal spread. If there was a real risk of contamination from (say) surgical instrumentation (as there was with vCJD in the UK) there would be extensive evidence for this (just in terms of a numbers game). Which isn&#x27;t to say if you put someone&#x27;s brain in your brain you won&#x27;t develop the disease, but at that point you probably have bigger issues to worry about...<p>In my opinion, a much more exciting story relating to ALS was published in Cell a couple of days ago;<p>Patel, A., Lee, H. O., Jawerth, L., Maharana, S., Jahnel, M., Hein, M. Y., … Alberti, S. (2015). A Liquid-to-Solid Phase Transition of the ALS Protein FUS Accelerated by Disease Mutation. Cell, 162(5), 1066–1077.<p>[1] <a href="http:&#x2F;&#x2F;www.ncbi.nlm.nih.gov&#x2F;pmc&#x2F;articles&#x2F;PMC3942086&#x2F;" rel="nofollow">http:&#x2F;&#x2F;www.ncbi.nlm.nih.gov&#x2F;pmc&#x2F;articles&#x2F;PMC3942086&#x2F;</a><p>[2] <a href="http:&#x2F;&#x2F;www.ncbi.nlm.nih.gov&#x2F;pubmed&#x2F;24857020" rel="nofollow">http:&#x2F;&#x2F;www.ncbi.nlm.nih.gov&#x2F;pubmed&#x2F;24857020</a><p>[3] <a href="http:&#x2F;&#x2F;jem.rupress.org&#x2F;content&#x2F;209&#x2F;5&#x2F;889.full" rel="nofollow">http:&#x2F;&#x2F;jem.rupress.org&#x2F;content&#x2F;209&#x2F;5&#x2F;889.full</a><p>[4] <a href="http:&#x2F;&#x2F;www.ncbi.nlm.nih.gov&#x2F;pmc&#x2F;articles&#x2F;PMC3820001&#x2F;" rel="nofollow">http:&#x2F;&#x2F;www.ncbi.nlm.nih.gov&#x2F;pmc&#x2F;articles&#x2F;PMC3820001&#x2F;</a>