Details of Disease

General Information of Disease (ID: DISTHQI1)

• Disease Name: Amyotrophic lateral sclerosis-parkinsonism-dementia complex
• Synonyms: amyotrophic lateral sclerosis-PARKINSONISM/dementia complex 1; amyotrophic lateral sclerosis-parkinsonism/dementia complex, susceptibility to; amyotrophic lateral sclerosis, Parkinsonism/dementia complex of Guam; ALS-pDC; amyotrophic lateral sclerosis-Parkinsonism/dementia Complex of Guam; amyotrophic lateral sclerosis-Parkinsonism/dementia Complex type 1; PDALS; Lytigo-Bodig disease; Guam disease; amyotrophic lateral sclerosis-parkinsonism-dementia of Guam syndrome; Lytico-Bodig disease; Parkinsonism-dementia-ALS complex
• Disease Hierarchy:
  DISPN7D2: Inherited neurodegenerative disorder
  DISTHQI1: Amyotrophic lateral sclerosis-parkinsonism-dementia complex
• Disease Identifiers:
  MONDO ID: MONDO_0007104
  MESH ID: D000690
  UMLS CUI: C0543859
  OMIM ID: 105500
  MedGen ID: 107775
  Orphanet ID: 90020
  SNOMED CT ID: 838276009

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 19 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
C9orf72	TTA4SHR	Limited	Biomarker	[1]
TRPM7	TTFPVZO	Limited	Unknown	[2]
SIGMAR1	TT5TPI6	moderate	Biomarker	[3]
ATXN2	TTPQJ7P	Strong	Biomarker	[4]
CD40LG	TTIJP3Q	Strong	Therapeutic	[5]
FUS	TTKGYZ9	Strong	Biomarker	[6]
GFAP	TTI6FFX	Strong	Biomarker	[7]
GSTP1	TT40K12	Strong	Biomarker	[8]
MOBP	TTYUK4F	Strong	Biomarker	[9]
NEK1	TTO5QT2	Strong	Biomarker	[10]
PLA2G4A	TTT1JVS	Strong	Biomarker	[11]
PON1	TT9LX82	Strong	Biomarker	[12]
SLC1A2	TT2F078	Strong	Biomarker	[7]
SLC6A1	TTPRKM0	Strong	Biomarker	[13]
SOD1	TTP9K3Q	Strong	Biomarker	[14]
SQSTM1	TTOT2RY	Strong	Biomarker	[15]
TARDBP	TT9RZ03	Strong	Biomarker	[16]
TNFRSF21	TT8UA0T	Strong	Biomarker	[17]
GSR	TTEP6RV	Definitive	Biomarker	[18]

This Disease Is Related to 9 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
TRPM7	OTHG1J2G	Limited	Unknown	[2]
IGFALS	OTTWCZYM	moderate	Biomarker	[19]
CAMK1G	OT1VEDLV	Strong	Biomarker	[20]
CFAP410	OTJ94J99	Strong	Biomarker	[9]
CHMP2B	OTZA7RJB	Strong	Biomarker	[21]
DBR1	OTLTWLTE	Strong	Therapeutic	[22]
DPP6	OTWW3H0K	Strong	Biomarker	[23]
OPTN	OT2UXWH9	Strong	Biomarker	[24]
SCFD1	OTN4T7JI	Strong	Biomarker	[9]

References

• [1] Genetic variation associated with the occurrence and progression of neurological disorders.Neurotoxicology. 2017 Jul;61:243-264. doi: 10.1016/j.neuro.2016.09.018. Epub 2016 Oct 3.
• [2] A TRPM7 variant shows altered sensitivity to magnesium that may contribute to the pathogenesis of two Guamanian neurodegenerative disorders. Proc Natl Acad Sci U S A. 2005 Aug 9;102(32):11510-5. doi: 10.1073/pnas.0505149102. Epub 2005 Jul 28.
• [3] Lack of synergistic effect of resveratrol and sigma-1 receptor agonist (PRE-084) in SOD1GA ALS mice: overlapping effects or limited therapeutic opportunity?.Orphanet J Rare Dis. 2014 May 21;9:78. doi: 10.1186/1750-1172-9-78.
• [4] Identification of risk factors associated with onset and progression of amyotrophic lateral sclerosis using systematic review and meta-analysis.Neurotoxicology. 2017 Jul;61:101-130. doi: 10.1016/j.neuro.2016.06.015. Epub 2016 Jul 1.
• [5] From transcriptome analysis to therapeutic anti-CD40L treatment in the SOD1 model of amyotrophic lateral sclerosis.Nat Genet. 2010 May;42(5):392-9. doi: 10.1038/ng.557. Epub 2010 Mar 28.
• [6] ALS mutations of FUS suppress protein translation and disrupt the regulation of nonsense-mediated decay.Proc Natl Acad Sci U S A. 2018 Dec 18;115(51):E11904-E11913. doi: 10.1073/pnas.1810413115. Epub 2018 Nov 19.
• [7] Transgenic SOD1 G93A mice develop reduced GLT-1 in spinal cord without alterations in cerebrospinal fluid glutamate levels.J Neurochem. 2001 Nov;79(4):737-46. doi: 10.1046/j.1471-4159.2001.00572.x.
• [8] Activity and expression of glutathione S-transferase pi in patients with amyotrophic lateral sclerosis.Clin Chim Acta. 2006 Feb;364(1-2):217-21. doi: 10.1016/j.cccn.2005.07.008. Epub 2005 Aug 18.
• [9] Genome-wide association analyses identify new risk variants and the genetic architecture of amyotrophic lateral sclerosis. Nat Genet. 2016 Sep;48(9):1043-8. doi: 10.1038/ng.3622. Epub 2016 Jul 25.
• [10] NEK1 mutations in familial amyotrophic lateral sclerosis.Brain. 2016 May;139(Pt 5):e28. doi: 10.1093/brain/aww033. Epub 2016 Mar 5.
• [11] Integrative role of cPLA with COX-2 and the effect of non-steriodal anti-inflammatory drugs in a transgenic mouse model of amyotrophic lateral sclerosis.J Neurochem. 2005 Apr;93(2):403-11. doi: 10.1111/j.1471-4159.2005.03024.x.
• [12] Organophosphate neurotoxicity to the voluntary motor system on the trail of environment-caused amyotrophic lateral sclerosis: the known, the misknown, and the unknown.Arch Toxicol. 2017 Aug;91(8):2939-2952. doi: 10.1007/s00204-016-1926-1. Epub 2017 Jan 9.
• [13] In vitro activation of GAT1 transporters expressed in spinal cord gliosomes stimulates glutamate release that is abnormally elevated in the SOD1/G93A(+) mouse model of amyotrophic lateral sclerosis.J Neurochem. 2010 Apr;113(2):489-501. doi: 10.1111/j.1471-4159.2010.06628.x. Epub 2010 Feb 1.
• [14] Resveratrol treatment reduces the vulnerability of SH-SY5Y cells and cortical neurons overexpressing SOD1-G93A to Thimerosal toxicity through SIRT1/DREAM/PDYN pathway.Neurotoxicology. 2019 Mar;71:6-15. doi: 10.1016/j.neuro.2018.11.009. Epub 2018 Nov 29.
• [15] Sequestosome 1/p62 links familial ALS mutant SOD1 to LC3 via an ubiquitin-independent mechanism.J Neurochem. 2009 Nov;111(4):1062-73. doi: 10.1111/j.1471-4159.2009.06388.x. Epub 2009 Sep 18.
• [16] A high-content screen identifies novel compounds that inhibit stress-induced TDP-43 cellular aggregation and associated cytotoxicity. J Biomol Screen. 2014 Jan;19(1):44-56. doi: 10.1177/1087057113501553. Epub 2013 Sep 9.
• [17] Death receptor 6 (DR6) antagonist antibody is neuroprotective in the mouse SOD1G93A model of amyotrophic lateral sclerosis.Cell Death Dis. 2013 Oct 10;4(10):e841. doi: 10.1038/cddis.2013.378.
• [18] Alterations in anti-oxidative defence enzymes in erythrocytes from sporadic amyotrophic lateral sclerosis (SALS) and familial ALS patients. Clin Chem Lab Med. 2006;44(5):589-93.
• [19] Intrathecal infusion of BMAA induces selective motor neuron damage and astrogliosis in the ventral horn of the spinal cord.Exp Neurol. 2014 Nov;261:1-9. doi: 10.1016/j.expneurol.2014.06.003. Epub 2014 Jun 8.
• [20] Genome-wide association analyses in Han Chinese identify two new susceptibility loci for amyotrophic lateral sclerosis.Nat Genet. 2013 Jun;45(6):697-700. doi: 10.1038/ng.2627. Epub 2013 Apr 28.
• [21] ALS phenotypes with mutations in CHMP2B (charged multivesicular body protein 2B). Neurology. 2006 Sep 26;67(6):1074-7. doi: 10.1212/01.wnl.0000231510.89311.8b. Epub 2006 Jun 28.
• [22] Inhibition of RNA lariat debranching enzyme suppresses TDP-43 toxicity in ALS disease models.Nat Genet. 2012 Dec;44(12):1302-9. doi: 10.1038/ng.2434. Epub 2012 Oct 28.
• [23] Genetic variation in DPP6 is associated with susceptibility to amyotrophic lateral sclerosis.Nat Genet. 2008 Jan;40(1):29-31. doi: 10.1038/ng.2007.52. Epub 2007 Dec 16.
• [24] Optineurin associates with the podocyte Golgi complex to maintain its structure.Cell Tissue Res. 2014 Nov;358(2):567-83. doi: 10.1007/s00441-014-1968-8. Epub 2014 Aug 7.