| H00058 | |
| H number | H00058 |
| Name | Amyotrophic lateral sclerosis (ALS); Lou Gehrig disease |
| Description | Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by a progressive degeneration of motor neurons in the brain and spinal cord. In 90% of patients, ALS is sporadic, with no clear genetic linkage. On the other hand, the remaining 10% of cases show familial inheritance, with mutations in SOD1, TDP43(TARDBP), FUS, or C9orf72 genes being the most frequent causes. In spite of such difference, familial ALS and sporadic ALS have similarities in their pathological features. Proposed disease mechanisms contributing to motor neuron degeneration in ALS are: impaired proteostasis, aberrant RNA processing, mitochondrial disfunction and oxidative stress, microglia activation, and axonal dysfunction. |
| Category | Neurodegenerative disease DIS_PATHWAY hsa05014 Amyotrophic lateral sclerosis |
| Network | nt06464 Amyotrophic lateral sclerosis nt06515(H00058) Regulation of kinetochore-microtubule interactions nt06530(H00058) PI3K signaling |
| Gene | (ALS1) SOD1 [HSA:6647] [KO:K04565] (ALS1) NEFH [HSA:4744] [KO:K04574] (ALS1) PRPH [HSA:5630] [KO:K07607] (ALS1) DCTN1 [HSA:1639] [KO:K04648] (ALS2) ALS2 [HSA:57679] [KO:K04575] (ALS4) SETX [HSA:23064] [KO:K10706] (ALS5) SPG11 [HSA:80208] [KO:K19026] (ALS6) FUS [HSA:2521] [KO:K13098] (ALS8) VAPB [HSA:9217] [KO:K10707] (ALS9) ANG [HSA:283] [KO:K16631] (ALS10) TARDBP [HSA:23435] [KO:K23600] (ALS11) FIG4 [HSA:9896] [KO:K22913] (ALS12) OPTN [HSA:10133] [KO:K19946] (ALS15) UBQLN2 [HSA:29978] [KO:K04523] (ALS16) SIGMAR1 [HSA:10280] [KO:K20719] (ALS18) PFN1 [HSA:5216] [KO:K05759] (ALS19) ERBB4 [HSA:2066] [KO:K05085] (ALS20) HNRNPA1 [HSA:3178] [KO:K12741] (ALS21) MATR3 [HSA:9782] [KO:K13213] (ALS22) TUBA4A [HSA:7277] [KO:K07374] (ALS23) ANXA11 [HSA:311] [KO:K17095] (ALS24) NEK1 [HSA:4750] [KO:K08857] (ALS25) KIF5A [HSA:3798] [KO:K10396] (ALS26) TIA1 [HSA:7072] [KO:K13201] (ALS27) SPTLC1 [HSA:10558] [KO:K00654] (ALS28) LRP12 [HSA:29967] [KO:K20050] (ALSPDC) TRPM7 [HSA:54822] [KO:K04982] (ALSPDC) MAPT [HSA:4137] [KO:K04380] |
| Pathogen | - |
| Env factor | - |
| Carcinogen | - |
| Drug | Riluzole [DR:D00775] Edaravone [DR:D01552] Tofersen [DR:D11811] (SOD1 mutated) Sodium phenylbutyrate and taurursodiol [DR:D12439] |
| Comment | Affected region: motor cortex, brain stem, spinal cord Microscopic lesion: hyaline inclusions |
| Other DBs | ICD-11: 8B60.0 ICD-10: G12.2 MeSH: D000690 OMIM: 105400 205100 602433 602099 608030 608627 611895 612069 612577 613435 300857 614373 614808 615515 615426 606070 617839 616208 617839 617892 617921 619133 620285 620452 105500 |
| Reference | PMID:28980624 AUTHORS Hardiman O, Al-Chalabi A, Chio A, Corr EM, Logroscino G, Robberecht W, Shaw PJ, Simmons Z, van den Berg LH TITLE Amyotrophic lateral sclerosis. JOURNAL Nat Rev Dis Primers 3:17071 (2017) DOI:10.1038/nrdp.2017.71 PMID:26213621 AUTHORS Yamashita S, Ando Y TITLE Genotype-phenotype relationship in hereditary amyotrophic lateral sclerosis. JOURNAL Transl Neurodegener 4:13 (2015) DOI:10.1186/s40035-015-0036-y PMID:15952898 (ALS1) AUTHORS Valentine JS, Doucette PA, Zittin Potter S TITLE Copper-zinc superoxide dismutase and amyotrophic lateral sclerosis. JOURNAL Annu Rev Biochem 74:563-93 (2005) DOI:10.1146/annurev.biochem.72.121801.161647 PMID:15106121 (ALS4) AUTHORS Chen YZ, Bennett CL, Huynh HM, Blair IP, Puls I, Irobi J, Dierick I, Abel A, Kennerson ML, Rabin BA, Nicholson GA, Auer-Grumbach M, Wagner K, De Jonghe P, Griffin JW, Fischbeck KH, Timmerman V, Cornblath DR, Chance PF TITLE DNA/RNA helicase gene mutations in a form of juvenile amyotrophic lateral sclerosis (ALS4). JOURNAL Am J Hum Genet 74:1128-35 (2004) DOI:10.1086/421054 PMID:19251628 (ALS6) AUTHORS Vance C, Rogelj B, Hortobagyi T, De Vos KJ, Nishimura AL, Sreedharan J, Hu X, Smith B, Ruddy D, Wright P, Ganesalingam J, Williams KL, Tripathi V, Al-Saraj S, Al-Chalabi A, Leigh PN, Blair IP, Nicholson G, de Belleroche J, Gallo JM, Miller CC, Shaw CE TITLE Mutations in FUS, an RNA processing protein, cause familial amyotrophic lateral sclerosis type 6. JOURNAL Science 323:1208-11 (2009) DOI:10.1126/science.1165942 PMID:16501576 (ALS9) AUTHORS Greenway MJ, Andersen PM, Russ C, Ennis S, Cashman S, Donaghy C, Patterson V, Swingler R, Kieran D, Prehn J, Morrison KE, Green A, Acharya KR, Brown RH Jr, Hardiman O TITLE ANG mutations segregate with familial and 'sporadic' amyotrophic lateral sclerosis. JOURNAL Nat Genet 38:411-3 (2006) DOI:10.1038/ng1742 PMID:18802454 (ALS10) AUTHORS Rutherford NJ, Zhang YJ, Baker M, Gass JM, Finch NA, Xu YF, Stewart H, Kelley BJ, Kuntz K, Crook RJ, Sreedharan J, Vance C, Sorenson E, Lippa C, Bigio EH, Geschwind DH, Knopman DS, Mitsumoto H, Petersen RC, Cashman NR, Hutton M, Shaw CE, Boylan KB, Boeve B, Graff-Radford NR, Wszolek ZK, Caselli RJ, Dickson DW, Mackenzie IR, Petrucelli L, Rademakers R TITLE Novel mutations in TARDBP (TDP-43) in patients with familial amyotrophic lateral sclerosis. JOURNAL PLoS Genet 4:e1000193 (2008) DOI:10.1371/journal.pgen.1000193 PMID:19118816 (ALS11) AUTHORS Chow CY, Landers JE, Bergren SK, Sapp PC, Grant AE, Jones JM, Everett L, Lenk GM, McKenna-Yasek DM, Weisman LS, Figlewicz D, Brown RH, Meisler MH TITLE Deleterious variants of FIG4, a phosphoinositide phosphatase, in patients with ALS. JOURNAL Am J Hum Genet 84:85-8 (2009) DOI:10.1016/j.ajhg.2008.12.010 PMID:20428114 (ALS12) AUTHORS Maruyama H, Morino H, Ito H, Izumi Y, Kato H, Watanabe Y, Kinoshita Y, Kamada M, Nodera H, Suzuki H, Komure O, Matsuura S, Kobatake K, Morimoto N, Abe K, Suzuki N, Aoki M, Kawata A, Hirai T, Kato T, Ogasawara K, Hirano A, Takumi T, Kusaka H, Hagiwara K, Kaji R, Kawakami H TITLE Mutations of optineurin in amyotrophic lateral sclerosis. JOURNAL Nature 465:223-6 (2010) DOI:10.1038/nature08971 PMID:30870681 (ALS1-ALS23) AUTHORS Mathis S, Goizet C, Soulages A, Vallat JM, Masson GL TITLE Genetics of amyotrophic lateral sclerosis: A review. JOURNAL J Neurol Sci 399:217-226 (2019) DOI:10.1016/j.jns.2019.02.030 PMID:26945885 (ALS24) AUTHORS Brenner D, Muller K, Wieland T, Weydt P, Bohm S, Lule D, Hubers A, Neuwirth C, Weber M, Borck G, Wahlqvist M, Danzer KM, Volk AE, Meitinger T, Strom TM, Otto M, Kassubek J, Ludolph AC, Andersen PM, Weishaupt JH TITLE NEK1 mutations in familial amyotrophic lateral sclerosis. JOURNAL Brain 139:e28 (2016) DOI:10.1093/brain/aww033 PMID:29566793 (ALS25) AUTHORS Nicolas A, Kenna KP, Renton AE, Ticozzi N, Faghri F, Chia R, Dominov JA, Kenna BJ, Nalls MA, Keagle P, Rivera AM, van Rheenen W, Murphy NA, van Vugt JJFA, Geiger JT, Van der Spek RA, Pliner HA, Shankaracharya, Smith BN, Marangi G, Topp SD, Abramzon Y, Gkazi AS, Eicher JD, Kenna A, Mora G, Calvo A, Mazzini L, Riva N, Mandrioli J, Caponnetto C, Battistini S, Volanti P, La Bella V, Conforti FL, Borghero G, Messina S, Simone IL, Trojsi F, Salvi F, Logullo FO, D'Alfonso S, Corrado L, Capasso M, Ferrucci L, Moreno CAM, Kamalakaran S, Goldstein DB, Gitler AD, Harris T, Myers RM, Phatnani H, Musunuri RL, Evani US, Abhyankar A, Zody MC, Kaye J, Finkbeiner S, Wyman SK, LeNail A, Lima L, Fraenkel E, Svendsen CN, Thompson LM, Van Eyk JE, Berry JD, Miller TM, Kolb SJ, Cudkowicz M, Baxi E, Benatar M, Taylor JP, Rampersaud E, Wu G, Wuu J, Lauria G, Verde F, Fogh I, Tiloca C, Comi GP, Soraru G, Cereda C, Corcia P, Laaksovirta H, Myllykangas L, Jansson L, Valori M, Ealing J, Hamdalla H, Rollinson S, Pickering-Brown S, Orrell RW, Sidle KC, Malaspina A, Hardy J, Singleton AB, Johnson JO, Arepalli S, Sapp PC, McKenna-Yasek D, Polak M, Asress S, Al-Sarraj S, King A, Troakes C, Vance C, de Belleroche J, Baas F, Ten Asbroek ALMA, Munoz-Blanco JL, Hernandez DG, Ding J, Gibbs JR, Scholz SW, Floeter MK, Campbell RH, Landi F, Bowser R, Pulst SM, Ravits JM, MacGowan DJL, Kirby J, Pioro EP, Pamphlett R, Broach J, Gerhard G, Dunckley TL, Brady CB, Kowall NW, Troncoso JC, Le Ber I, Mouzat K, Lumbroso S, Heiman-Patterson TD, Kamel F, Van Den Bosch L, Baloh RH, Strom TM, Meitinger T, Shatunov A, Van Eijk KR, de Carvalho M, Kooyman M, Middelkoop B, Moisse M, McLaughlin RL, Van Es MA, Weber M, Boylan KB, Van Blitterswijk M, Rademakers R, Morrison KE, Basak AN, Mora JS, Drory VE, Shaw PJ, Turner MR, Talbot K, Hardiman O, Williams KL, Fifita JA, Nicholson GA, Blair IP, Rouleau GA, Esteban-Perez J, Garcia-Redondo A, Al-Chalabi A, Rogaeva E, Zinman L, Ostrow LW, Maragakis NJ, Rothstein JD, Simmons Z, Cooper-Knock J, Brice A, Goutman SA, Feldman EL, Gibson SB, Taroni F, Ratti A, Gellera C, Van Damme P, Robberecht W, Fratta P, Sabatelli M, Lunetta C, Ludolph AC, Andersen PM, Weishaupt JH, Camu W, Trojanowski JQ, Van Deerlin VM, Brown RH Jr, van den Berg LH, Veldink JH, Harms MB, Glass JD, Stone DJ, Tienari P, Silani V, Chio A, Shaw CE, Traynor BJ, Landers JE TITLE Genome-wide Analyses Identify KIF5A as a Novel ALS Gene. JOURNAL Neuron 97:1268-1283.e6 (2018) DOI:10.1016/j.neuron.2018.02.027 PMID:28817800 (ALS26) AUTHORS Mackenzie IR, Nicholson AM, Sarkar M, Messing J, Purice MD, Pottier C, Annu K, Baker M, Perkerson RB, Kurti A, Matchett BJ, Mittag T, Temirov J, Hsiung GR, Krieger C, Murray ME, Kato M, Fryer JD, Petrucelli L, Zinman L, Weintraub S, Mesulam M, Keith J, Zivkovic SA, Hirsch-Reinshagen V, Roos RP, Zuchner S, Graff-Radford NR, Petersen RC, Caselli RJ, Wszolek ZK, Finger E, Lippa C, Lacomis D, Stewart H, Dickson DW, Kim HJ, Rogaeva E, Bigio E, Boylan KB, Taylor JP, Rademakers R TITLE TIA1 Mutations in Amyotrophic Lateral Sclerosis and Frontotemporal Dementia Promote Phase Separation and Alter Stress Granule Dynamics. JOURNAL Neuron 95:808-816.e9 (2017) DOI:10.1016/j.neuron.2017.07.025 PMID:34059824 (ALS27) AUTHORS Mohassel P, Donkervoort S, Lone MA, Nalls M, Gable K, Gupta SD, Foley AR, Hu Y, Saute JAM, Moreira AL, Kok F, Introna A, Logroscino G, Grunseich C, Nickolls AR, Pourshafie N, Neuhaus SB, Saade D, Gangfuss A, Kolbel H, Piccus Z, Le Pichon CE, Fiorillo C, Ly CV, Topf A, Brady L, Specht S, Zidell A, Pedro H, Mittelmann E, Thomas FP, Chao KR, Konersman CG, Cho MT, Brandt T, Straub V, Connolly AM, Schara U, Roos A, Tarnopolsky M, Hoke A, Brown RH, Lee CH, Hornemann T, Dunn TM, Bonnemann CG TITLE Childhood amyotrophic lateral sclerosis caused by excess sphingolipid synthesis. JOURNAL Nat Med 27:1197-1204 (2021) DOI:10.1038/s41591-021-01346-1 PMID:37339631 (ALS28) AUTHORS Kume K, Kurashige T, Muguruma K, Morino H, Tada Y, Kikumoto M, Miyamoto T, Akutsu SN, Matsuda Y, Matsuura S, Nakamori M, Nishiyama A, Izumi R, Niihori T, Ogasawara M, Eura N, Kato T, Yokomura M, Nakayama Y, Ito H, Nakamura M, Saito K, Riku Y, Iwasaki Y, Maruyama H, Aoki Y, Nishino I, Izumi Y, Aoki M, Kawakami H TITLE CGG repeat expansion in LRP12 in amyotrophic lateral sclerosis. JOURNAL Am J Hum Genet 110:1086-1097 (2023) DOI:10.1016/j.ajhg.2023.05.014 PMID:16051700 (ALSPDC) AUTHORS Hermosura MC, Nayakanti H, Dorovkov MV, Calderon FR, Ryazanov AG, Haymer DS, Garruto RM TITLE A TRPM7 variant shows altered sensitivity to magnesium that may contribute to the pathogenesis of two Guamanian neurodegenerative disorders. JOURNAL Proc Natl Acad Sci U S A 102:11510-5 (2005) DOI:10.1073/pnas.0505149102 PMID:17185385 (ALSPDC) AUTHORS Sundar PD, Yu CE, Sieh W, Steinbart E, Garruto RM, Oyanagi K, Craig UK, Bird TD, Wijsman EM, Galasko DR, Schellenberg GD TITLE Two sites in the MAPT region confer genetic risk for Guam ALS/PDC and dementia. JOURNAL Hum Mol Genet 16:295-306 (2007) DOI:10.1093/hmg/ddl463 PMID:29403345 (ALSPDC) AUTHORS Hata Y, Ma N, Yoneda M, Morimoto S, Okano H, Murayama S, Kawanishi S, Kuzuhara S, Kokubo Y TITLE Nitrative Stress and Tau Accumulation in Amyotrophic Lateral Sclerosis/Parkinsonism-Dementia Complex (ALS/PDC) in the Kii Peninsula, Japan. JOURNAL Front Neurosci 11:751 (2017) DOI:10.3389/fnins.2017.00751 |