title: Mechanisms of Membrane Pore Formation by Amyloidogenic Peptides in Amyotrophic Lateral Sclerosis.
abstract: 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.
authors.affiliation: Department of Materials Science and Engineering, Johns Hopkins University, 3400 North Charles Street, Baltimore, MD, 21218-2608, USA.
authors.forename: Charles H
authors.initials: CH
authors.lastname: Chen
authors.affiliation: Institute for NanoBioTechnology, Johns Hopkins University, 3400 North Charles Street, Baltimore, MD, 21218-2608, USA.
authors.forename: Ayesha
authors.initials: A
authors.lastname: Khan
authors.affiliation: Institute of Chemistry, Academia Sinica, 128 Academia Road Sec. 2, Nankang Taipei, 115 Taiwan, ROC.
authors.forename: Joseph Jen-Tse
authors.initials: JJ
authors.lastname: Huang
authors.affiliation: Department of Materials Science and Engineering, Johns Hopkins University, 3400 North Charles Street, Baltimore, MD, 21218-2608, USA. martin@ulmschneider.com.|Institute for NanoBioTechnology, Johns Hopkins University, 3400 North Charles Street, Baltimore, MD, 21218-2608, USA. martin@ulmschneider.com.
authors.forename: Martin B
authors.initials: MB
authors.lastname: Ulmschneider
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000378:metabolism; D008051:Lipid Bilayers / Q000737:chemistry*; D008565:Membrane Proteins / Q000737:chemistry*; D056004:Molecular Dynamics Simulation; D010455:Peptides / Q000737:chemistry*; D014867:Water / Q000737:chemistry*
chemical_list: D004268:DNA-Binding Proteins; D008051:Lipid Bilayers; D008565:Membrane Proteins; D010455:Peptides; D014867:Water
keywords: amyotrophic lateral sclerosis; membranes; molecular dynamics simulations; neurotoxicity; peptide aggregation