“It is well known that the thermodynamically stable state of proteins in a crowded environment is insoluble fibrils” [ Proc. Natl. Acad. Sci. vol. 119 pp. e2122078119 ’22 ]. However even under ideal conditions the time scale for their formation is hours to days [ Nat. Rev. Mol. Cell Biol. 15, 384–396 (2014) ]. Hopefully it’s even longer (decades) for senile plaques (abeta) neurofibrils (tau) and Lewy bodies (alpha-synuclein) to form. The fact that equilibrium takes such a long time to reach, allows rapid synthesis and degradation of proteins to avoid their aggregation. So we live because our proteins are trapped in a less the equilibrium (metastable) state by kinetics — e.g. a kinetic trap.
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