KEGG   DISEASE: Amyotrophic lateral sclerosis (ALS)
Entry
H00058                      Disease                                
Name
Amyotrophic lateral sclerosis (ALS);
Lou Gehrig disease
  Subgroup
Frontotemporal dementia and amyotrophic lateral sclerosis [DS:H02342]
Amyotrophic lateral sclerosis and Parkinsonism-dementia complex (ALSPDC)
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
Brite
Human diseases [BR:br08402]
 Nervous system diseases
  Neurodegenerative diseases
   H00058  Amyotrophic lateral sclerosis (ALS)
Human diseases in ICD-11 classification [BR:br08403]
 08 Diseases of the nervous system
  Motor neuron diseases or related disorders
   8B60  Motor neuron disease
    H00058  Amyotrophic lateral sclerosis (ALS)
Pathway
hsa05014  Amyotrophic lateral sclerosis
Network
nt06464  Amyotrophic lateral sclerosis
nt06515  Regulation of kinetochore-microtubule interactions
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]
(ALSPDC) TRPM7 [HSA:54822] [KO:K04982]
(ALSPDC) MAPT [HSA:4137] [KO:K04380]
Drug
Riluzole [DR:D00775]
Edaravone [DR:D01552]
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 105500 617892 617921 619133
Reference
  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
Reference
  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
Reference
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
Reference
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
Reference
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
Reference
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
Reference
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
Reference
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
Reference
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
Reference
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
Reference
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
Reference
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
Reference
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
Reference
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
Reference
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
Reference
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
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