Entry
Name
Amyotrophic lateral sclerosis - Mustela putorius furo (domestic ferret)
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.
Class
Human Diseases; Neurodegenerative disease
BRITE hierarchy
Pathway map
Ortholog table
Organism
Mustela putorius furo (domestic ferret) [GN:
mpuf ]
Gene
101679801 NDUFV3; NADH dehydrogenase [ubiquinone] flavoprotein 3, mitochondrial [KO:K03944 ]
101683103 NDUFA1; NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 1 [KO:K03945 ]
101681305 NDUFA2; NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 2 [KO:K03946 ]
101671885 NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 3-like [KO:K03947 ]
101678258 NDUFA3; NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 3 [KO:K03947 ]
101678946 NDUFA4L2; NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 4-like 2 [KO:K03948 ]
101688416 NDUFA5; NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 5 [KO:K03949 ]
101673253 NDUFA6; NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 6 [KO:K03950 ]
101686920 NDUFA7; NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 7 [KO:K03951 ]
101675000 NDUFA8; NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 8 [KO:K03952 ]
101680168 NDUFA9; NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 9, mitochondrial [KO:K03953 ]
101693615 NDUFA10; NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 10, mitochondrial [KO:K03954 ]
101684673 NDUFA11; NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 11 [KO:K03956 ]
101674482 NDUFA12; NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 12 [KO:K11352 ]
101679389 NDUFA13; LOW QUALITY PROTEIN: NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 13 [KO:K11353 ]
101694062 NDUFB1; NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 1 [KO:K03957 ]
101674641 NDUFB2; NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 2, mitochondrial isoform X2 [KO:K03958 ]
101683892 NDUFB3; NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 3 [KO:K03959 ]
101691663 NDUFB4; NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 4 [KO:K03960 ]
101687434 NDUFB5; NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 5, mitochondrial [KO:K03961 ]
101688606 NDUFB6; NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 6 [KO:K03962 ]
101675882 NDUFB7; NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 7 [KO:K03963 ]
101675804 NDUFB8; NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 8, mitochondrial [KO:K03964 ]
101682240 NDUFB9; NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 9 isoform X1 [KO:K03965 ]
101681324 NDUFB10; NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 10 [KO:K03966 ]
101682983 NDUFB11; NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 11, mitochondrial [KO:K11351 ]
101688652 NDUFS2; NADH dehydrogenase [ubiquinone] iron-sulfur protein 2, mitochondrial [KO:K03935 ] [EC:7.1.1.2 ]
101686313 NDUFS3; NADH dehydrogenase [ubiquinone] iron-sulfur protein 3, mitochondrial [KO:K03936 ] [EC:7.1.1.2 ]
101674933 NDUFS4; NADH dehydrogenase [ubiquinone] iron-sulfur protein 4, mitochondrial [KO:K03937 ]
101684469 NDUFS5; NADH dehydrogenase [ubiquinone] iron-sulfur protein 5 [KO:K03938 ]
101692362 NADH dehydrogenase [ubiquinone] iron-sulfur protein 6, mitochondrial-like [KO:K03939 ]
101688718 NDUFS6; NADH dehydrogenase [ubiquinone] iron-sulfur protein 6, mitochondrial [KO:K03939 ]
101674706 NDUFS7; NADH dehydrogenase [ubiquinone] iron-sulfur protein 7, mitochondrial [KO:K03940 ] [EC:7.1.1.2 ]
101679983 NDUFS8; NADH dehydrogenase [ubiquinone] iron-sulfur protein 8, mitochondrial isoform X1 [KO:K03941 ] [EC:7.1.1.2 ]
101691647 NDUFC1; NADH dehydrogenase [ubiquinone] 1 subunit C1, mitochondrial [KO:K03967 ]
101678731 SDHA; succinate dehydrogenase [ubiquinone] flavoprotein subunit, mitochondrial [KO:K00234 ] [EC:1.3.5.1 ]
101692858 SDHB; succinate dehydrogenase [ubiquinone] iron-sulfur subunit, mitochondrial [KO:K00235 ] [EC:1.3.5.1 ]
101685355 LOW QUALITY PROTEIN: succinate dehydrogenase cytochrome b560 subunit, mitochondrial-like [KO:K00236 ]
101680264 SDHC; succinate dehydrogenase cytochrome b560 subunit, mitochondrial [KO:K00236 ]
101694292 SDHD; succinate dehydrogenase [ubiquinone] cytochrome b small subunit, mitochondrial [KO:K00237 ]
101685926 LOW QUALITY PROTEIN: cytochrome b-c1 complex subunit 2, mitochondrial-like [KO:K00415 ]
101681748 cytochrome b-c1 complex subunit 6, mitochondrial isoform X1 [KO:K00416 ]
101680163 cytochrome c oxidase subunit 4 isoform 1, mitochondrial [KO:K02263 ]
101676075 cytochrome c oxidase subunit 4 isoform 2, mitochondrial isoform X1 [KO:K02263 ]
101672219 cytochrome c oxidase subunit 7A-related protein, mitochondrial [KO:K02270 ]
101689814 ATP5C1; ATP synthase subunit gamma, mitochondrial isoform X1 [KO:K02136 ]
101683533 ATP5F1; ATP synthase F(0) complex subunit B1, mitochondrial [KO:K02127 ]
101672934 ATP5G1; ATP synthase F(0) complex subunit C1, mitochondrial isoform X1 [KO:K02128 ]
101673943 ATP5G2; LOW QUALITY PROTEIN: ATP synthase F(0) complex subunit C2, mitochondrial [KO:K02128 ]
106005210 LOW QUALITY PROTEIN: uncharacterized protein LOC106005210 [KO:K02128 ]
106006495 LOW QUALITY PROTEIN: ATP synthase F(0) complex subunit C2, mitochondrial-like [KO:K02128 ]
101690076 ATP5G3; ATP synthase F(0) complex subunit C3, mitochondrial [KO:K02128 ]
101679422 VDAC1; voltage-dependent anion-selective channel protein 1 [KO:K05862 ]
101678959 TOMM40L; mitochondrial import receptor subunit TOM40B [KO:K11518 ]
101680015 TOMM40; mitochondrial import receptor subunit TOM40 homolog [KO:K11518 ]
101679131 MCU; calcium uniporter protein, mitochondrial isoform X1 [KO:K20858 ]
101675711 MAP1LC3B; microtubule-associated proteins 1A/1B light chain 3B [KO:K10435 ]
101675872 MAP1LC3A; microtubule-associated proteins 1A/1B light chain 3A [KO:K10435 ]
101694085 TANK; TRAF family member-associated NF-kappa-B activator isoform X1 [KO:K12650 ]
101670526 SMCR8; Smith-Magenis syndrome chromosomal region candidate gene 8 protein [KO:K23611 ]
101692151 RB1CC1; RB1-inducible coiled-coil protein 1 isoform X1 [KO:K17589 ]
101680997 AMBRA1; activating molecule in BECN1-regulated autophagy protein 1 isoform X1 [KO:K17985 ]
101684646 ATG14; beclin 1-associated autophagy-related key regulator [KO:K17889 ]
101691773 ATG2B; autophagy-related protein 2 homolog B isoform X1 [KO:K17906 ]
101674575 ATG2A; autophagy-related protein 2 homolog A isoform X2 [KO:K17906 ]
101688271 WIPI2; WD repeat domain phosphoinositide-interacting protein 2 [KO:K17908 ]
101676578 WIPI1; WD repeat domain phosphoinositide-interacting protein 1 [KO:K17908 ]
101693834 RAC1; ras-related C3 botulinum toxin substrate 1 isoform X1 [KO:K04392 ]
101692520 FIG4; polyphosphoinositide phosphatase isoform X1 [KO:K22913 ] [EC:3.1.3.-]
101675854 PPP3CC; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform isoform X1 [KO:K04348 ] [EC:3.1.3.16 ]
101675984 PPP3CB; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform isoform X1 [KO:K04348 ] [EC:3.1.3.16 ]
101682554 PPP3CA; serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform isoform X1 [KO:K04348 ] [EC:3.1.3.16 ]
101692211 VCP; transitional endoplasmic reticulum ATPase isoform X1 [KO:K13525 ]
101689832 PSMC6; 26S protease regulatory subunit 10B isoform X1 [KO:K03064 ]
101679423 PSMD2; 26S proteasome non-ATPase regulatory subunit 2 [KO:K03028 ]
101677647 PSMD1; 26S proteasome non-ATPase regulatory subunit 1 [KO:K03032 ]
101689542 PSMD3; 26S proteasome non-ATPase regulatory subunit 3 [KO:K03033 ]
101681801 PSMD9; 26S proteasome non-ATPase regulatory subunit 9 [KO:K06693 ]
101682559 PSMD12; 26S proteasome non-ATPase regulatory subunit 12 [KO:K03035 ]
101682352 PSMD11; 26S proteasome non-ATPase regulatory subunit 11 [KO:K03036 ]
101670551 PSMD6; 26S proteasome non-ATPase regulatory subunit 6 [KO:K03037 ]
101690051 PSMD7; 26S proteasome non-ATPase regulatory subunit 7 [KO:K03038 ]
101674526 PSMD13; 26S proteasome non-ATPase regulatory subunit 13 isoform X2 [KO:K03039 ]
101672325 PSMD4; 26S proteasome non-ATPase regulatory subunit 4 [KO:K03029 ]
101670572 PSMD14; 26S proteasome non-ATPase regulatory subunit 14 [KO:K03030 ]
101687128 PSMD8; 26S proteasome non-ATPase regulatory subunit 8 [KO:K03031 ]
106003941 heterogeneous nuclear ribonucleoprotein A1-like isoform X1 [KO:K12741 ]
101692078 heterogeneous nuclear ribonucleoproteins A2/B1 isoform X1 [KO:K13158 ]
101692283 HNRNPA2B1; heterogeneous nuclear ribonucleoproteins A2/B1 isoform X1 [KO:K13158 ]
101684208 NCBP1; nuclear cap-binding protein subunit 1 isoform X1 [KO:K12882 ]
101679222 SRSF7; serine/arginine-rich splicing factor 7 isoform X1 [KO:K12896 ]
101672206 NUP98; nuclear pore complex protein Nup98-Nup96 isoform X4 [KO:K14297 ]
101691126 NUP107; nuclear pore complex protein Nup107 isoform X1 [KO:K14301 ]
101673640 NUP62CL; nucleoporin-62 C-terminal-like protein isoform X1 [KO:K14306 ]
101691820 NUP205; nuclear pore complex protein Nup205 isoform X1 [KO:K14310 ]
101682122 NUP210L; nuclear pore membrane glycoprotein 210-like isoform X2 [KO:K14314 ]
101678899 POM121C; nuclear envelope pore membrane protein POM 121C isoform X1 [KO:K14316 ]
101688383 NUP214; nuclear pore complex protein Nup214 isoform X1 [KO:K14317 ]
101679310 RANBP2; E3 SUMO-protein ligase RanBP2 isoform X2 [KO:K12172 ] [EC:2.3.2.-]
101691540 CHCHD10; coiled-coil-helix-coiled-coil-helix domain-containing protein 10, mitochondrial [KO:K22759 ]
101691521 VAPB; vesicle-associated membrane protein-associated protein B/C isoform X1 [KO:K10707 ]
101689116 ATF6; cyclic AMP-dependent transcription factor ATF-6 alpha [KO:K09054 ]
101689747 EIF2AK3; LOW QUALITY PROTEIN: eukaryotic translation initiation factor 2-alpha kinase 3 [KO:K08860 ] [EC:2.7.11.1 ]
101692556 EIF2S1; eukaryotic translation initiation factor 2 subunit 1 [KO:K03237 ]
101680524 ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374 ]
101676562 TNFRSF1A; tumor necrosis factor receptor superfamily member 1A [KO:K03158 ]
101689344 TNFRSF1B; tumor necrosis factor receptor superfamily member 1B [KO:K05141 ]
101679788 CCS; copper chaperone for superoxide dismutase isoform X1 [KO:K04569 ]
101692651 DNALI1; axonemal dynein light intermediate polypeptide 1 [KO:K10410 ]
101679241 DNAI1; dynein intermediate chain 1, axonemal isoform X2 [KO:K10409 ]
101687335 SLC1A2; excitatory amino acid transporter 2 isoform X1 [KO:K05613 ]
101683487 GRIN1; glutamate receptor ionotropic, NMDA 1 isoform X1 [KO:K05208 ]
101672107 GRIN2A; glutamate receptor ionotropic, NMDA 2A isoform X1 [KO:K05209 ]
101685410 NRG1; pro-neuregulin-1, membrane-bound isoform isoform X1 [KO:K05455 ]
Compound
C04549 1-Phosphatidyl-1D-myo-inositol 3-phosphate
Reference
Authors
Brown RH, Al-Chalabi A
Title
Amyotrophic Lateral Sclerosis.
Journal
Reference
Authors
Webster CP, Smith EF, Shaw PJ, De Vos KJ
Title
Protein Homeostasis in Amyotrophic Lateral Sclerosis: Therapeutic Opportunities?
Journal
Reference
Authors
Valko K, Ciesla L
Title
Amyotrophic lateral sclerosis.
Journal
Reference
Authors
Mathis S, Goizet C, Soulages A, Vallat JM, Masson GL
Title
Genetics of amyotrophic lateral sclerosis: A review.
Journal
Reference
Authors
Turner MR, Hardiman O, Benatar M, Brooks BR, Chio A, de Carvalho M, Ince PG, Lin C, Miller RG, Mitsumoto H, Nicholson G, Ravits J, Shaw PJ, Swash M, Talbot K, Traynor BJ, Van den Berg LH, Veldink JH, Vucic S, Kiernan MC
Title
Controversies and priorities in amyotrophic lateral sclerosis.
Journal
Reference
Authors
Pasinelli P, Brown RH
Title
Molecular biology of amyotrophic lateral sclerosis: insights from genetics.
Journal
Reference
Authors
Goodall EF, Morrison KE
Title
Amyotrophic lateral sclerosis (motor neuron disease): proposed mechanisms and pathways to treatment.
Journal
Reference
Authors
Smith EF, Shaw PJ, De Vos KJ
Title
The role of mitochondria in amyotrophic lateral sclerosis.
Journal
Reference
Authors
Kodavati M, Wang H, Hegde ML
Title
Altered Mitochondrial Dynamics in Motor Neuron Disease: An Emerging Perspective.
Journal
Reference
Authors
Hervias I, Beal MF, Manfredi G
Title
Mitochondrial dysfunction and amyotrophic lateral sclerosis.
Journal
Reference
Authors
Bacman SR, Bradley WG, Moraes CT
Title
Mitochondrial involvement in amyotrophic lateral sclerosis: trigger or target?
Journal
Reference
Authors
Lin MT, Beal MF
Title
Mitochondrial dysfunction and oxidative stress in neurodegenerative diseases.
Journal
Reference
Authors
Bendotti C, Bao Cutrona M, Cheroni C, Grignaschi G, Lo Coco D, Peviani M, Tortarolo M, Veglianese P, Zennaro E
Title
Inter- and intracellular signaling in amyotrophic lateral sclerosis: role of p38 mitogen-activated protein kinase.
Journal
Reference
Authors
Simpson EP, Yen AA, Appel SH
Title
Oxidative Stress: a common denominator in the pathogenesis of amyotrophic lateral sclerosis.
Journal
Reference
Authors
Bendotti C, Carri MT
Title
Lessons from models of SOD1-linked familial ALS.
Journal
Reference
Authors
Robertson J, Kriz J, Nguyen MD, Julien JP
Title
Pathways to motor neuron degeneration in transgenic mouse models.
Journal
Reference
Authors
Eve DJ, Dennis JS, Citron BA
Title
Transcription factor p53 in degenerating spinal cords.
Journal
Reference
Authors
Bahar E, Kim H, Yoon H
Title
ER Stress-Mediated Signaling: Action Potential and Ca(2+) as Key Players.
Journal
Reference
Authors
Bezprozvanny I
Title
Calcium signaling and neurodegenerative diseases.
Journal
Reference
Authors
von Lewinski F, Keller BU
Title
Ca2+, mitochondria and selective motoneuron vulnerability: implications for ALS.
Journal
Reference
Authors
Julien JP.
Title
Amyotrophic lateral sclerosis. unfolding the toxicity of the misfolded.
Journal
Reference
Authors
Hand CK, Rouleau GA
Title
Familial amyotrophic lateral sclerosis.
Journal
Reference
Authors
Barber SC, Mead RJ, Shaw PJ
Title
Oxidative stress in ALS: a mechanism of neurodegeneration and a therapeutic target.
Journal
Reference
Authors
Prasad A, Bharathi V, Sivalingam V, Girdhar A, Patel BK
Title
Molecular Mechanisms of TDP-43 Misfolding and Pathology in Amyotrophic Lateral Sclerosis.
Journal
Reference
Authors
Nguyen DKH, Thombre R, Wang J
Title
Autophagy as a common pathway in amyotrophic lateral sclerosis.
Journal
Reference
Authors
Lee JK, Shin JH, Lee JE, Choi EJ
Title
Role of autophagy in the pathogenesis of amyotrophic lateral sclerosis.
Journal
Reference
Authors
Oakes JA, Davies MC, Collins MO
Title
TBK1: a new player in ALS linking autophagy and neuroinflammation.
Journal
Reference
Authors
Ramesh N, Pandey UB
Title
Autophagy Dysregulation in ALS: When Protein Aggregates Get Out of Hand.
Journal
Reference
Authors
Kunita R, Otomo A, Mizumura H, Suzuki-Utsunomiya K, Hadano S, Ikeda JE
Title
The Rab5 activator ALS2/alsin acts as a novel Rac1 effector through Rac1-activated endocytosis.
Journal
Reference
Authors
Hadano S, Kunita R, Otomo A, Suzuki-Utsunomiya K, Ikeda JE
Title
Molecular and cellular function of ALS2/alsin: implication of membrane dynamics in neuronal development and degeneration.
Journal
Reference
Authors
Ruffoli R, Bartalucci A, Frati A, Fornai F
Title
Ultrastructural studies of ALS mitochondria connect altered function and permeability with defects of mitophagy and mitochondriogenesis.
Journal
Reference
Authors
Menzies FM, Fleming A, Rubinsztein DC
Title
Compromised autophagy and neurodegenerative diseases.
Journal
Reference
Authors
Casterton RL, Hunt RJ, Fanto M
Title
Pathomechanism Heterogeneity in the Amyotrophic Lateral Sclerosis and Frontotemporal Dementia Disease Spectrum: Providing Focus Through the Lens of Autophagy.
Journal
Reference
Authors
Lin G, Mao D, Bellen HJ
Title
Amyotrophic Lateral Sclerosis Pathogenesis Converges on Defects in Protein Homeostasis Associated with TDP-43 Mislocalization and Proteasome-Mediated Degradation Overload.
Journal
Reference
Authors
Hetz C, Mollereau B
Title
Disturbance of endoplasmic reticulum proteostasis in neurodegenerative diseases.
Journal
Reference
Authors
Xiang C, Wang Y, Zhang H, Han F
Title
The role of endoplasmic reticulum stress in neurodegenerative disease.
Journal
Reference
Authors
Hughes D, Mallucci GR
Title
The unfolded protein response in neurodegenerative disorders - therapeutic modulation of the PERK pathway.
Journal
Reference
Authors
Doyle KM, Kennedy D, Gorman AM, Gupta S, Healy SJ, Samali A
Title
Unfolded proteins and endoplasmic reticulum stress in neurodegenerative disorders.
Journal
Reference
Authors
Turner BJ, Atkin JD
Title
ER stress and UPR in familial amyotrophic lateral sclerosis.
Journal
Reference
Authors
Nishitoh H, Kadowaki H, Nagai A, Maruyama T, Yokota T, Fukutomi H, Noguchi T, Matsuzawa A, Takeda K, Ichijo H
Title
ALS-linked mutant SOD1 induces ER stress- and ASK1-dependent motor neuron death by targeting Derlin-1.
Journal
Reference
Authors
Walker AK, Atkin JD
Title
Stress signaling from the endoplasmic reticulum: A central player in the pathogenesis of amyotrophic lateral sclerosis.
Journal
Reference
Authors
Renaud L, Picher-Martel V, Codron P, Julien JP
Title
Key role of UBQLN2 in pathogenesis of amyotrophic lateral sclerosis and frontotemporal dementia.
Journal
Reference
Authors
Nguyen HP, Van Broeckhoven C, van der Zee J
Title
ALS Genes in the Genomic Era and their Implications for FTD.
Journal
Reference
Authors
Atkin G, Paulson H
Title
Ubiquitin pathways in neurodegenerative disease.
Journal
Reference
Authors
Kim JM, Billington E, Reyes A, Notarianni T, Sage J, Agbas E, Taylor M, Monast I, Stanford JA, Agbas A
Title
Impaired Cu-Zn Superoxide Dismutase (SOD1) and Calcineurin (Cn) Interaction in ALS: A Presumed Consequence for TDP-43 and Zinc Aggregation in Tg SOD1(G93A) Rodent Spinal Cord Tissue.
Journal
Reference
Authors
Benarroch EE
Title
Sigma-1 receptor and amyotrophic lateral sclerosis.
Journal
Reference
Authors
Millecamps S, Julien JP
Title
Axonal transport deficits and neurodegenerative diseases.
Journal
Related pathway
mpuf04141 Protein processing in endoplasmic reticulum
KO pathway
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