Decoding ALS: from genes to mechanism.
Amyotrophic lateral sclerosis (ALS) is a progressive and uniformly fatal neurodegenerative disease. A plethora of genetic factors have been identified that drive the degeneration of motor neurons in ALS, increase susceptibility to the disease or influence the rate of its progression. Emerging themes include dysfunction in RNA metabolism and protein homeostasis, with specific defects in nucleocytoplasmic trafficking, the induction of stress at the endoplasmic reticulum and impaired dynamics of ribonucleoprotein bodies such as RNA granules that assemble through liquid-liquid phase separation. Extraordinary progress in understanding the biology of ALS provides new reasons for optimism that meaningful therapies will be identified.
Howard Hughes Medical Institute and the Department of Cell and Molecular Biology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA.
J Paul
JP
Taylor
Department of Neurology, University of Massachusetts Medical School, Worcester, Massachusetts 01655, USA.
Robert H
RH
Brown
Ludwig Institute for Cancer Research, University of California, San Diego, La Jolla, California 92093, USA.|Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, California 92093, USA.
Don W
DW
Cleveland
D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology* / Q000628:therapy; D000818:Animals; D001692:Biological Transport; D000073885:C9orf72 Protein; D059865:Endoplasmic Reticulum Stress / Q000235:genetics; D057180:Frontotemporal Dementia / Q000235:genetics; D006801:Humans; D009420:Nervous System / Q000473:pathology / Q000503:physiopathology; D015388:Organelles / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D011328:Prions / Q000378:metabolism; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D059748:Proteolysis; D012313:RNA / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism / Q000633:toxicity
D000073885:C9orf72 Protein; C568651:C9orf72 protein, human; D011328:Prions; D011506:Proteins; D012313:RNA