Fig. 1

Timeline of gene discovery and pathogenic mechanisms in ALS. Schematic representation of years of discovery of most important genes implicated in ALS. Mutation in the superoxide dismutase 1 (SOD1) represent approximately 15 % of familial ALS cases (fALS), mutation in C9orf72 represent 35-40 % and both TAR-DNA-binding protein (TARDBP) and Fused in sarcoma (FUS) for 4 % each. Other genes represent less than 1 % each. Protein aggregation and gliosis are pathological hallmark of ALS and have been discovered before the beginning of the illustrated timeline. ER endoplasmic reticulum; NEFH neurofilament heavy; ALS2 alsin; DCTN1 dynactin; PRPH peripherin; SETX senataxin; VAPB vesicle-associated membrane protein-associated protein B; CHMP2B Charged multivesicular body protein 2B; ANG angiogenin; FIG4 phosphoinositide 5-phosphatase; OPTN optineurin; ATXN2 ataxin 2; DAO D-amino acid oxidase; SPG11 spastic paraplegia 11; VCP valosin containing protein; SIGMAR1 sigma non-opioid intracellular receptor 1; TAF15 TATA-box binding protein associated factor 15; UBQLN2 ubiquilin-2; SQSTM1 sequestosome 1; PFN1 profilin-1; HNRNPA1 heterogeneous nuclear ribonucleoprotein A1; ERBB4 erb-2 receptor tyrosine kinase 4; MATR3 matrin 3; TUBA4A tubulin alpha-4a; TBK1 TANK-binding kinase 1