The final version is out! Viruses lead to untemplated amyloid formation of proteins in human cerebrospinal fluid even after UV-inactivation, resulting in a drastic depletion of soluble proteins. 1/6
pubs.acs.org/doi/10.1021/ac… The resistance of amyloidogenic agents to UV inactivation was the foundation of the protein-only prion hypothesis. We show that, while UV inactivates viral nucleic acids, it does not affect the ability of viruses to act as catalytic surfaces that induce amyloid aggregation. 2/6

An important paper in @Nature from the influential @MRC_LMB in Cambridge with very imp. points. 1. "The models for templated seeding may need reconsidering". This is a big deal. A strong & clear criticism of conformational templating, the foundation of the prion hypothesis. 1/8

https://twitter.com/SjorsScheres/status/1707065755475288264

This is done after citing the experimental evidence from numerous papers where templating fails to occur + the dominant nature of 2ry nucleation on fibril surfaces during amyloid growth where templating is impossible. More explanation here: 2/8

https://x.com/Kariem_Ezzat/status/1629505966084431874?s=20

Our new book chapter where we elaborate more on physicochemical principles that govern amyloid aggregation. We propose that a simple extension of the thermodynamic hypothesis of protein folding (Anfinsen's dogma) to supersaturated conditions can ..1/10 sciencedirect.com/science/articl… ..fully explain the amyloid phenomenon without the need for the prion hypothesis. We postulate that proteins possess two thermodynamically stable conformations: 1. The native conformation, which is dependent on the primary sequence & is thermodynamically favorable under..2/10

A new study confirming & expanding on the strong epidemiological link between viruses & neurodegenerative diseases (NDDs). There's no real reason to exclude viruses from NDD etiology, especially in relation to the ability of viruses to induce amyloid..1/8
cell.com/neuron/fulltex… ..aggregation. This is where the "protein-only" hypothesis is most damaging imo, by necessitating (with no real biophysical mechanism) the unnecessary process of prion conformational templating. Protein conformations do not require templating, since proteins adopt..2/8

Our new preprint showing that viruses such as HSV-1 & #SARSCoV2 can induce amyloid aggregation proteins in human CSF. Viruses act as nucleation catalysts for amyloid formation, which is driven by protein supersaturation, not conformational templating. 1/7
biorxiv.org/content/10.110… This is why no prion/protein template was required to obtain these results & UV-inactivation didn’t affect the ability of the viruses to act as nucleation catalysts. While UV-inactivation destroys viral nucleic acids, it does not affect the ability of viruses to act as..2/7

Comparing the success in disease-modifying therapies for SMA to the failure in #Huntington's (HD) can be illuminating. Two successful SMA medications, a small molecule: risdiplam & an oligo: nusinersen, both restore SMN protein levels. For HD, two medications that worsened..1/5 ..the disease, a small molecule: branaplam & an oligo: tominersen, both reduced the huntingtin protein levels. Different molecules & different mechanisms, but in the end replacement works in neurodegeneration & protein downregulation worsens the disease. The puzzling part is..2/5