Antiviral Immune Response as a Trigger of FUS Proteinopathy in Amyotrophic Lateral Sclerosis

• Published in: Cell reports (Cambridge) Vol. 29; no. 13; pp. 4496 - 4508.e4
• Main Authors: Shelkovnikova, Tatyana A., An, Haiyan, Skelt, Lucy, Tregoning, John S., Humphreys, Ian R., Buchman, Vladimir L.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 24.12.2019; Cell Press; Elsevier
• Subjects: Active Transport, Cell Nucleus - genetics; Active Transport, Cell Nucleus - immunology; ALS; amyotrophic lateral sclerosis; Amyotrophic Lateral Sclerosis - immunology; Amyotrophic Lateral Sclerosis - metabolism; Amyotrophic Lateral Sclerosis - pathology; Amyotrophic Lateral Sclerosis - virology; antiviral response; Cell Cycle Proteins - genetics; Cell Cycle Proteins - immunology; Cell Line; Cytoplasmic Granules - genetics; Cytoplasmic Granules - immunology; Cytoplasmic Granules - virology; dopamine; dsRNA; Fibroblasts - cytology; Fibroblasts - drug effects; Fibroblasts - immunology; FUS; FUS proteinopathy; fused in sarcoma; Gene Expression Regulation; Host-Pathogen Interactions - drug effects; Host-Pathogen Interactions - genetics; Host-Pathogen Interactions - immunology; Humans; Inclusion Bodies - genetics; Inclusion Bodies - immunology; Inclusion Bodies - virology; Interferon Type I - genetics; Interferon Type I - immunology; Male; Membrane Transport Proteins - genetics; Membrane Transport Proteins - immunology; Motor Neurons - immunology; Motor Neurons - metabolism; Motor Neurons - virology; Neuroglia - immunology; Neuroglia - metabolism; Neuroglia - virology; nucleocytoplasmic transport; Nucleocytoplasmic Transport Proteins - genetics; Nucleocytoplasmic Transport Proteins - immunology; optineurin; Poly I-C - pharmacology; Primary Cell Culture; Protein Aggregates - genetics; Protein Aggregates - immunology; Respiratory Syncytial Virus; Respiratory Syncytial Viruses - immunology; Respiratory Syncytial Viruses - pathogenicity; RNA granule; RNA Stability; RNA, Messenger - genetics; RNA, Messenger - immunology; RNA-Binding Protein FUS - genetics; RNA-Binding Protein FUS - immunology; Spinal Cord - immunology; Spinal Cord - metabolism; Spinal Cord - pathology; Spinal Cord - virology; stress granule; dsRNA; Respiratory Syncytial Virus; FUS; stress granule; RNA granule; ALS; FUS proteinopathy; amyotrophic lateral sclerosis; fused in sarcoma; antiviral response; optineurin; nucleocytoplasmic transport; dopamine

Mutations in the FUS gene cause familial amyotrophic lateral sclerosis (ALS-FUS). In ALS-FUS, FUS-positive inclusions are detected in the cytoplasm of neurons and glia, a condition known as FUS proteinopathy. Mutant FUS incorporates into stress granules (SGs) and can spontaneously form cytoplasmic R...