Luk KC, Kehm V, Carroll J, Zhang B, O'Brien P, Trojanowski JQ, Lee VM.
Pathological α-synuclein transmission initiates Parkinson-like neurodegeneration in nontransgenic mice.
Science. 2012 Nov 16;338(6109):949-53.
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This is a very important paper that further supports the role of a prion-like propagation of proteins involved in neurodegenerative disorders. This is the first study that has been able to show propagation of α-synuclein after a single injection in non-transgenic wild-type animals; this is rather remarkable.
Previous studies have shown propagation, but in α-synuclein transgenic mice. Others have tried to propagate synuclein in non-transgenic mice but encountered difficulties. Thus, the question arises as to what is unique in this study by the group of Virginia Lee. One possibility is the characteristics of the α-synuclein seeds they developed. They might represent a strain more prone to propagate than others. Such seed strain properties have been shown for the prion protein.
These are very impressive results from Virginia Lee and colleagues, and build on the previous work of the same group. The fact that synthetic material can act as a seed in wild-type mice opens a myriad of experimental approaches and avoids confounding factors such as overexpression of host proteins and the necessity of using brain-derived material as seed. This work will further advance the understanding of the propagation and spreading of protein misfolding diseases. It is becoming increasingly clear that protein aggregates associated with neurodegenerative disorders are found to have prion-like properties and, once misfolded, initiate a cascade of corruptive templating and related pathology: common mechanism, common amyloid principles (Eisenberg and Jucker, 2012).
Eisenberg D, Jucker M.
The amyloid state of proteins in human diseases.
Cell. 2012 Mar 16;148(6):1188-203.
This is an impressive result, agreed. Just would like to point out that the most likely and earliest entry point for an exogenous process would be through the olfactory bulb, not the gut. Our thorough survey of the peripheral nervous system in subjects with PD, DLB, ADLB, and ILBD, as well as aged normal controls, found no case where peripheral nervous system synucleinopathy was present in the absence of central nervous system synucleinopathy.
Beach TG, Adler CH, Sue LI, Vedders L, Lue L, White Iii CL, Akiyama H, Caviness JN, Shill HA, Sabbagh MN, Walker DG, .
Multi-organ distribution of phosphorylated alpha-synuclein histopathology in subjects with Lewy body disorders.
Acta Neuropathol. 2010 Jun;119(6):689-702.