Mechanisms of Membrane Pore Formation by Amyloidogenic Peptides in Amyotrophic Lateral Sclerosis.

Using unbiased atomic-detailed molecular dynamics simulations, the C-terminal fragments of TDP-43 are observed to aggregate and form disordered-toroidal pores in a lipid bilayer. Cytotoxicity of TDP-43 may be inferred from the observation that the membrane pores catalyze lipid flip-flop between bilayer leaflets and conduct water at high rates.