KEGG DISEASE: Amyotrophic lateral sclerosis (ALS)

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)

Disease
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

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

Reference

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

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

» Japanese version

All links

Pathway (1)   
   KEGG PATHWAY (1)   
Network (40)   
   KEGG NETWORK (24)   
   KEGG VARIANT (16)   
Disease (22)   
   OMIM (22)   
Drug (8)   
   KEGG DRUG (8)   
Gene (52)   
   KEGG ORTHOLOGY (26)   
   KEGG GENES (26)   
Literature (16)   
   PubMed (16)   
All databases (139)   

Download RDF

DBGET integrated database retrieval system