Mutations in the vesicular trafficking protein annexin A11 are associated with amyotrophic lateral sclerosis.
Bradley N. Smith,Simon Topp,Claudia Fallini,Hideki Shibata,Han-Jou Chen,Claire Troakes,Andrew P. King,Nicola Ticozzi,Kevin P. Kenna,Athina Soragia-Gkazi,Jack W. Miller,Akane Sato,Diana Marques Dias,Maryangel Jeon,Caroline Vance,Chun Hao Wong,Martina de Majo,Wejdan Kattuah,Jacqueline C. Mitchell,Emma L. Scotter,Nicholas W Parkin,Peter C. Sapp,Matthew Nolan,Peter J. Nestor,Michael A. Simpson,Michael E. Weale,Monkel Lek,Monkel Lek,Frank Baas,J M Vianney de Jong,Anneloor L.M.A. ten Asbroek,Alberto Garcia Redondo,Jesús Esteban-Pérez,Cinzia Tiloca,Federico Verde,Stefano Duga,Nigel Leigh,Hardev Pall,Karen E. Morrison,Ammar Al-Chalabi,Pamela J. Shaw,Janine Kirby,Martin R Turner,Kevin Talbot,Orla Hardiman,Jonathan D. Glass,Jacqueline de Belleroche,Masatoshi Maki,Stephen E. Moss,Christopher C.J. Miller,Cinzia Gellera,Antonia Ratti,Safa Al-Sarraj,Robert H. Brown,Vincenzo Silani,John Landers,Christopher Shaw +56 more
TLDR
It is concluded that mutations in ANXA11 are associated with ALS and implicate defective intracellular protein trafficking in disease pathogenesis.Abstract:
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder. We screened 751 familial ALS patient whole-exome sequences and identified six mutations including p.D40G in the ANXA11 gene in 13 individuals. The p.D40G mutation was absent from 70,000 control whole-exome sequences. This mutation segregated with disease in two kindreds and was present in another two unrelated cases (P = 0.0102), and all mutation carriers shared a common founder haplotype. Annexin A11–positive protein aggregates were abundant in spinal cord motor neurons and hippocampal neuronal axons in an ALS patient carrying the p.D40G mutation. Transfected human embryonic kidney cells expressing ANXA11 with the p.D40G mutation and other N-terminal mutations showed altered binding to calcyclin, and the p.R235Q mutant protein formed insoluble aggregates. We conclude that mutations in ANXA11 are associated with ALS and implicate defective intracellular protein trafficking in disease pathogenesis.read more
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Delivery technologies for cancer immunotherapy
TL;DR: How recent developments in drug delivery could enable new cancer immunotherapies and improve on existing ones are discussed, and the current delivery obstacles are examined.
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Context-Dependent and Disease-Specific Diversity in Protein Interactions within Stress Granules.
Sebastian Markmiller,Sahar Soltanieh,Kari L. Server,Raymond H. Mak,Wenhao Jin,Mark Y. Fang,En-Ching Luo,Florian Krach,Dejun Yang,Anindya Sen,Amit Fulzele,Jacob M. Wozniak,David Gonzalez,David Gonzalez,Mark W. Kankel,Fen-Biao Gao,Eric J. Bennett,Eric Lécuyer,Gene W. Yeo +18 more
TL;DR: Stress granules (SGs) are transient ribonucleoprotein (RNP) aggregates that form during cellular stress and are increasingly implicated in human neurodegeneration as mentioned in this paper.
Journal ArticleDOI
RNA Granules Hitchhike on Lysosomes for Long-Distance Transport, Using Annexin A11 as a Molecular Tether.
Ya-Cheng Liao,Michael S. Fernandopulle,GuoZhen Wang,Heejun Choi,Ling Hao,Catherine M. Drerup,Rajan Patel,Seema Qamar,Jonathon Nixon-Abell,Yi Shen,William Meadows,Michele Vendruscolo,Tuomas P. J. Knowles,Matthew Nelson,Magdalena A. Czekalska,Greta Musteikyte,Mariam A. Gachechiladze,Christina A. Stephens,H. Amalia Pasolli,Lucy R. Forrest,Peter St George-Hyslop,Peter St George-Hyslop,Jennifer Lippincott-Schwartz,Michael E. Ward +23 more
TL;DR: This work presents a mechanism for RNA transport in which RNA granules “hitchhike” on moving lysosomes, and reveals that annexin A11 (ANXA11), an RNA granule-associated phosphoinositide-binding protein, acts as a molecular tether betweenRNA granules and lysOSomes.
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ALS Genes in the Genomic Era and their Implications for FTD
TL;DR: This review paper presents a comprehensive overview of recently proposed ALS genes that were identified based on rare genetic variants and their potential relevance to frontotemporal dementia genetic etiology and highlights emerging key molecular processes and opportunities for therapy.
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Toll-like Receptors and Inflammatory Bowel Disease.
TL;DR: The purpose of this review article is to summarize the potential mechanisms of TLR signaling pathways in IBD and the novel potential therapeutic strategies against IBD.
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