PURPOSE OF REVIEW: Amyotrophic lateral sclerosis (ALS), like other neurodegenerative diseases, remains incurable, but gene mutations linked to ALS are providing clues as to how to target therapies. It is important for researchers to keep abreast of the rapid influx of new data in ALS, and we aim to summarize the major genetic advances made in the field over the past 2 years. RECENT FINDINGS: Significant variation in seven genes has recently been found in ALS: TBK1, CCNF, GLE1, MATR3, TUBA4A, CHCHD10 and NEK1. These have mostly been identified through large exome screening studies, though traditional linkage approaches and candidate gene screening remain important. We briefly update C9orf72 research, noting in particular the development of reagents to better understand the normal role of C9orf72 protein. SUMMARY: Striking advances in our understanding of the genetic heterogeneity of ALS continue to be made, year on year. These implicate proteostasis, RNA export, nuclear transport, the cytoskeleton, mitochondrial function, the cell cycle and DNA repair. Functional studies to integrate these hits are needed. By building a web of knowledge with interlinked genes and mechanisms, it is hoped we can better understand ALS and work toward effective therapies.
PURPOSE OF REVIEW: Amyotrophic lateral sclerosis (ALS), like other neurodegenerative diseases, remains incurable, but gene mutations linked to ALS are providing clues as to how to target therapies. It is important for researchers to keep abreast of the rapid influx of new data in ALS, and we aim to summarize the major genetic advances made in the field over the past 2 years. RECENT FINDINGS: Significant variation in seven genes has recently been found in ALS: TBK1, CCNF, GLE1, MATR3, TUBA4A, CHCHD10 and NEK1. These have mostly been identified through large exome screening studies, though traditional linkage approaches and candidate gene screening remain important. We briefly update C9orf72 research, noting in particular the development of reagents to better understand the normal role of C9orf72 protein. SUMMARY: Striking advances in our understanding of the genetic heterogeneity of ALS continue to be made, year on year. These implicate proteostasis, RNA export, nuclear transport, the cytoskeleton, mitochondrial function, the cell cycle and DNA repair. Functional studies to integrate these hits are needed. By building a web of knowledge with interlinked genes and mechanisms, it is hoped we can better understand ALS and work toward effective therapies.
Authors: Bradley N Smith; Simon D Topp; Claudia Fallini; Hideki Shibata; Han-Jou Chen; Claire Troakes; Andrew 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 Simpson; Michael Weale; 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 Miller; Cinzia Gellera; Antonia Ratti; Safa Al-Sarraj; Robert H Brown; Vincenzo Silani; John E Landers; Christopher E Shaw Journal: Sci Transl Med Date: 2017-05-03 Impact factor: 19.319