In summary, our data indicate for the first time and unequivocally, using in vitro, ex vivo and in vivo approaches that (i) prion-like Tau-seed induced Tau-aggregation with NFT formation a mechanism under intensive investigation causes synaptic and neuronal network dysfunction, resulting in behavioral impairments.
Besides, a major influence of the PrPc expression levels has been demonstrated in transgenic mice over-expressing (i) mutated human prion protein linked to Gerstmann Sträussler-Scheinker syndrome [37], [38] or (ii) a prion protein with a nine-octapeptide insertion associated with a human familial prion disease [39], [40].
The YJW679 strain lacked the [PIN+] prion i.e. was [pin−].
There is at least one previous example of a protein that mimics heparin, binds laminin, behaves as a basement membrane protein and binds prion, i.e. acetylcholine esterase [ 43].
The real definition of prion I guess is ability to propagate, more than its SDS insolubility.
We agree with the reviewer's last substantive point: "The real definition of prion I guess is ability to propagate, more than its SDS insolubility.
Due to this undirected nature, I would place prion formation to the weak end of the continuum concerning quasi-Lamarckian mode of evolution.
Conversely, no signal was evident when using healthy brain homogenates (columns 4, 8, 12 and 14), or cells incompetent for prion propagation (i.e. the N2a cell line) (Fig. 2, lower panels).
In the present study, we used infectious brain homogenate to study PrP adsorption and desorption as well as soil-bound prion replication (i.e. conversion of PrPc to PrPSc).
We tested a novel approach for tetracycline administration which permitted a more aggressive treatment schedule in a model of overt prion disease, i.e. ic inoculation of the 263K scrapie strain followed by intracereboventricular (icv) infusion of liposome-entrapped drugs.
On the one hand, this demonstrates the interest of such a simple biochemical test to refine PrP analysis, and on the other hand it raises a question about the existence of different PrPres signatures in the same patient, i.e., different prion strains linked to multiple infections or to variants selected by the host.
