TDP-43 or FUS-induced misfolded human wild-type SOD1 can propagate intercellularly in a prion-like fashion

• Published in: Scientific reports Vol. 6; no. 1; p. 22155
• Main Authors: Pokrishevsky, Edward, Grad, Leslie I., Cashman, Neil R.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.03.2016; Nature Publishing Group
• Subjects: 13/106; 14/63; 631/80/304; 631/92/609; 692/617/375/1917/1285; 82; 82/80; Amyotrophic lateral sclerosis; Amyotrophic Lateral Sclerosis - genetics; Amyotrophic Lateral Sclerosis - metabolism; Amyotrophic Lateral Sclerosis - pathology; Animals; Antibodies; Antibody Specificity; Culture Media, Conditioned; Cytotoxicity; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; FUS gene; FUS protein; Gene Knockdown Techniques; HEK293 Cells; Humanities and Social Sciences; Humans; Immunocytochemistry; Immunoprecipitation; Media; Mice; Mice, Transgenic; Motor neurons; Motor Neurons - metabolism; Motor Neurons - pathology; Motor task performance; multidisciplinary; Mutant Proteins - genetics; Mutant Proteins - metabolism; Mutation; Pathology; Prions - genetics; Prions - immunology; Prions - metabolism; Protein Folding; RNA, Small Interfering - genetics; RNA-Binding Protein FUS - genetics; RNA-Binding Protein FUS - metabolism; Science; siRNA; Superoxide dismutase; Superoxide Dismutase-1 - chemistry; Superoxide Dismutase-1 - genetics; Superoxide Dismutase-1 - metabolism

Amyotrophic lateral sclerosis (ALS), which appears to spread through the neuroaxis in a spatiotemporally restricted manner, is linked to heritable mutations in genes encoding SOD1, TDP-43, FUS, C9ORF72, or can occur sporadically without recognized genetic mutations. Misfolded human wild-type (HuWt)...