| Structural highlights
Disease
SODC_HUMAN Defects in SOD1 are the cause of amyotrophic lateral sclerosis type 1 (ALS1) [MIM:105400. ALS1 is a familial form of amyotrophic lateral sclerosis, a neurodegenerative disorder affecting upper and lower motor neurons and resulting in fatal paralysis. Sensory abnormalities are absent. Death usually occurs within 2 to 5 years. The etiology of amyotrophic lateral sclerosis is likely to be multifactorial, involving both genetic and environmental factors. The disease is inherited in 5-10% of cases leading to familial forms.[1] [2] [3] [4] [5] [6] [7] [8] [:][9] [10] [11] [12] [13] [14] [15] [16] [17] [18] [19] [20] [21] [22] [23] [24] [25] [26] [27] [28] [29] [30] [31] [32] [33] [34] [35] [36] [37] [38] [39] [40] [41] [42] [43] [44] [45]
Function
SODC_HUMAN Destroys radicals which are normally produced within the cells and which are toxic to biological systems.
Publication Abstract from PubMed
Amyotrophic lateral sclerosis (ALS) selectively affects motor neurons. SOD1 is the first causative gene to be identified for ALS and accounts for at least 20% of the familial (fALS) and up to 4% of sporadic (sALS) cases globally with some geographical variability. The destabilisation of the SOD1 dimer is a key driving force in fALS and sALS. Protein aggregation resulting from the destabilised SOD1 is arrested by the clinical drug ebselen and its analogues (MR6-8-2 and MR6-26-2) by redeeming the stability of the SOD1 dimer. The in vitro target engagement of these compounds is demonstrated using the bimolecular fluorescence complementation assay with protein-ligand binding directly visualised by co-crystallography in G93A SOD1. MR6-26-2 offers neuroprotection slowing disease onset of SOD1(G93A) mice by approximately 15 days. It also protected neuromuscular junction from muscle denervation in SOD1(G93A) mice clearly indicating functional improvement.
Ebselen analogues delay disease onset and its course in fALS by on-target SOD-1 engagement.,Watanabe S, Amporndanai K, Awais R, Latham C, Awais M, O'Neill PM, Yamanaka K, Hasnain SS Sci Rep. 2024 May 27;14(1):12118. doi: 10.1038/s41598-024-62903-5. PMID:38802492[46]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
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- ↑ Orrell RW, Marklund SL, deBelleroche JS. Familial ALS is associated with mutations in all exons of SOD1: a novel mutation in exon 3 (Gly72Ser). J Neurol Sci. 1997 Dec 9;153(1):46-9. PMID:9455977
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- ↑ Watanabe S, Amporndanai K, Awais R, Latham C, Awais M, O'Neill PM, Yamanaka K, Hasnain SS. Ebselen analogues delay disease onset and its course in fALS by on-target SOD-1 engagement. Sci Rep. 2024 May 27;14(1):12118. PMID:38802492 doi:10.1038/s41598-024-62903-5
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