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Amyotrophic lateral sclerosis

Disease ID:61
Name:Amyotrophic lateral sclerosis
Associated with:3 targets
Database Links
Disease Ontology: DOID:332
Orphanet: ORPHA803


C5a1 receptor
Comments:  In both the SODG93A and NFL-/- mouse models of ALS, C5aR is upregulated. The upregulation occurs in the presymptomatic stages of the NFL-/- model and the author observed this upregulation within motor neurons. However, in the SODG93A model, there is no early upregulation of C5aR within motor neurons, the upregulation occurs in the end stages of the model within motor neurons and astrocytes. The link between C5aR upregulation and ALS pathology has only been confirmed in the SODG93A model, where blockade of C5aR signalling with orally administered PMX205 increased survival and motor performance.
References:  1-2,4
Liver X receptor-α
NIMA related kinase 1
Role:  Loss of function NEK1 mutations and the Arg261His NEK1 variant have been identified as genetic factors which confer susceptibility to familial and sporadic amyotrophic lateral sclerosis. These risk variants were detected in 3% of ALS cases tested.
References:  3


No ligand related data available for Amyotrophic lateral sclerosis


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1. Ferraiuolo L, Heath PR, Holden H, Kasher P, Kirby J, Shaw PJ. (2007) Microarray analysis of the cellular pathways involved in the adaptation to and progression of motor neuron injury in the SOD1 G93A mouse model of familial ALS. J Neurosci, 27 (34): 9201-19. [PMID:17715356]

2. Humayun S, Gohar M, Volkening K, Moisse K, Leystra-Lantz C, Mepham J, McLean J, Strong MJ. (2009) The complement factor C5a receptor is upregulated in NFL-/- mouse motor neurons. J Neuroimmunol, 210 (1-2): 52-62. [PMID:19286267]

3. Kenna KP, van Doormaal PT, Dekker AM, Ticozzi N, Kenna BJ, Diekstra FP, van Rheenen W, van Eijk KR, Jones AR, Keagle P et al.. (2016) NEK1 variants confer susceptibility to amyotrophic lateral sclerosis. Nat Genet, 48 (9): 1037-42. [PMID:27455347]

4. Woodruff TM, Costantini KJ, Crane JW, Atkin JD, Monk PN, Taylor SM, Noakes PG. (2008) The complement factor C5a contributes to pathology in a rat model of amyotrophic lateral sclerosis. J Immunol, 181 (12): 8727-34. [PMID:19050293]