First synthetic mini prion shows how protein misfolding multiplies

Scientists at Northwestern University and University of California, Santa Barbara have created the first synthetic fragment of tau protein that acts like a prion.

The mini prion folds and stacks into strands (or fibrils) of misfolded tau proteins, which then transmit their abnormally folded shape to other normal tau proteins.

Misfolded, prion-like proteins drive the progression of tauopathies, a group of neurodegenerative diseases –including Alzheimer's disease – characterized by the abnormal accumulation of misfolded tau protein in the brain.

By studying a minimal synthetic version of the full-length human tau, scientists can better recreate the fibril structure containing misfolded tau proteins. This potentially could lead to targeted tools for diagnosis and therapy that are much needed for neurodegenerative diseases.

While developing the synthetic protein, the scientists also uncovered new insights into the role of water around the protein surface that guides the misfolding process.

Image source: Songi Han/Northwestern University.