. Kinetic model of the aggregation of alpha-synuclein provides insights into prion-like spreading. Proc Natl Acad Sci U S A. 2016 Mar 1;113(9):E1206-15. Epub 2016 Feb 16 PubMed.

Recommends

Please login to recommend the paper.

Comments

  1. I think this strategy has considerable value for clarifying how pathogenic protein molecules interact to cause disease. A key question, though, is where the proteins interact in the cell, since this could strongly influence the outcome. For instance, the lower pH in the endosome-lysosome system will be more favorable to certain aspects of protein aggregation. The findings also do not rule out a prion-like process, even in the presence of oxidative stress. A general increase in oxidative stress would be expected to increase the odds of many different proteins aggregating, not just α-synuclein. Oxidative stress might create a more conducive environment for seeding, and prion-like templating would explain the specificity for α-synuclein aggregation in this model. On the other hand, oxidative stress could account for some instances of apparent cross-seeding of one pathogenic protein by another.

Make a Comment

To make a comment you must login or register.