Editing Superoxide dismutase (section)

== Role in disease ==

Mutations in the first SOD enzyme ([[SOD1]]) can cause familial [[amyotrophic lateral sclerosis]] (ALS, a form of [[motor neuron disease]]).<ref name="pmid21603028">{{cite journal | vauthors = Milani P, Gagliardi S, Cova E, Cereda C | title = SOD1 Transcriptional and Posttranscriptional Regulation and Its Potential Implications in ALS | journal = Neurology Research International | volume = 2011 | pages = 458427 | year = 2011 | pmid = 21603028 | pmc = 3096450 | doi = 10.1155/2011/458427 | doi-access = free }}</ref><ref name="pmid8351519">{{cite journal | vauthors = Deng HX, Hentati A, Tainer JA, Iqbal Z, Cayabyab A, Hung WY, Getzoff ED, Hu P, Herzfeldt B, Roos RP | display-authors = 6 | title = Amyotrophic lateral sclerosis and structural defects in Cu,Zn superoxide dismutase | journal = Science | volume = 261 | issue = 5124 | pages = 1047–1051 | date = August 1993 | pmid = 8351519 | doi = 10.1126/science.8351519 | bibcode = 1993Sci...261.1047D }}</ref><ref name="pmid17070848">{{cite journal | vauthors = Conwit RA | title = Preventing familial ALS: a clinical trial may be feasible but is an efficacy trial warranted? | journal = Journal of the Neurological Sciences | volume = 251 | issue = 1–2 | pages = 1–2 | date = December 2006 | pmid = 17070848 | doi = 10.1016/j.jns.2006.07.009 | s2cid = 33105812 | url = https://zenodo.org/record/1259145 }}</ref><ref name="pmid10970056">{{cite journal | vauthors = Al-Chalabi A, Leigh PN | title = Recent advances in amyotrophic lateral sclerosis | journal = Current Opinion in Neurology | volume = 13 | issue = 4 | pages = 397–405 | date = August 2000 | pmid = 10970056 | doi = 10.1097/00019052-200008000-00006 | s2cid = 21577500 }}</ref> The most common mutation in the U.S. is [[SOD1#A4V|A4V]], while the most intensely studied is [[SOD1#G93A|G93A]]. Inactivation of SOD1 causes [[hepatocellular carcinoma]].<ref name="pmid15531919"/> Diminished SOD3 activity has been linked to lung diseases such as [[acute respiratory distress syndrome]] (ARDS) or [[chronic obstructive pulmonary disease]] (COPD).<ref name="pmid16467073">{{cite journal | vauthors = Young RP, Hopkins R, Black PN, Eddy C, Wu L, Gamble GD, Mills GD, Garrett JE, Eaton TE, Rees MI | display-authors = 6 | title = Functional variants of antioxidant genes in smokers with COPD and in those with normal lung function | journal = Thorax | volume = 61 | issue = 5 | pages = 394–399 | date = May 2006 | pmid = 16467073 | pmc = 2111196 | doi = 10.1136/thx.2005.048512 }}</ref><ref name="pmid19318538">{{cite journal | vauthors = Ganguly K, Depner M, Fattman C, Bein K, Oury TD, Wesselkamper SC, Borchers MT, Schreiber M, Gao F, von Mutius E, Kabesch M, Leikauf GD, Schulz H | display-authors = 6 | title = Superoxide dismutase 3, extracellular (SOD3) variants and lung function | journal = Physiological Genomics | volume = 37 | issue = 3 | pages = 260–267 | date = May 2009 | pmid = 19318538 | pmc = 2685504 | doi = 10.1152/physiolgenomics.90363.2008 }}</ref><ref name="pmid18787098">{{cite journal | vauthors = Gongora MC, Lob HE, Landmesser U, Guzik TJ, Martin WD, Ozumi K, Wall SM, Wilson DS, Murthy N, Gravanis M, Fukai T, Harrison DG | display-authors = 6 | title = Loss of extracellular superoxide dismutase leads to acute lung damage in the presence of ambient air: a potential mechanism underlying adult respiratory distress syndrome | journal = The American Journal of Pathology | volume = 173 | issue = 4 | pages = 915–926 | date = October 2008 | pmid = 18787098 | pmc = 2543061 | doi = 10.2353/ajpath.2008.080119 }}</ref> Superoxide dismutase is not expressed in neural crest cells in the developing [[fetus]]. Hence, high levels of free radicals can cause damage to them and induce dysraphic anomalies (neural tube defects).{{citation needed|date=May 2019}}

Mutations in [[SOD1]] can cause familial ALS (several pieces of evidence also show that wild-type SOD1, under conditions of cellular stress, is implicated in a significant fraction of sporadic ALS cases, which represent 90% of ALS patients.),<ref name="pmid20399857">{{cite journal | vauthors = Gagliardi S, Cova E, Davin A, Guareschi S, Abel K, Alvisi E, Laforenza U, Ghidoni R, Cashman JR, Ceroni M, Cereda C | display-authors = 6 | title = SOD1 mRNA expression in sporadic amyotrophic lateral sclerosis | journal = Neurobiology of Disease | volume = 39 | issue = 2 | pages = 198–203 | date = August 2010 | pmid = 20399857 | doi = 10.1016/j.nbd.2010.04.008 | s2cid = 207065284 }}</ref> by a mechanism that is presently not understood, but not due to loss of enzymatic activity or a decrease in the conformational stability of the SOD1 protein. Overexpression of SOD1 has been linked to the neural disorders seen in [[Down syndrome]].<ref name="pmid7999984">{{cite journal | vauthors = Groner Y, Elroy-Stein O, Avraham KB, Schickler M, Knobler H, Minc-Golomb D, Bar-Peled O, Yarom R, Rotshenker S | display-authors = 6 | title = Cell damage by excess CuZnSOD and Down's syndrome | journal = Biomedicine & Pharmacotherapy | volume = 48 | issue = 5–6 | pages = 231–240 | year = 1994 | pmid = 7999984 | doi = 10.1016/0753-3322(94)90138-4 }}</ref> In patients with thalassemia, SOD will increase as a form of compensation mechanism. However, in the chronic stage, SOD does not seem to be sufficient and tends to decrease due to the destruction of proteins from the massive reaction of oxidant-antioxidant.<ref>{{cite journal | vauthors = Rujito L, Mulatsih S, Sofro AS | title = Status of Superoxide Dismutase in Transfusion Dependent Thalassaemia | journal = North American Journal of Medical Sciences | volume = 7 | issue = 5 | pages = 194–198 | date = May 2015 | pmid = 26110130 | pmc = 4462814 | doi = 10.4103/1947-2714.157480 | doi-access = free }}</ref>

In mice, the extracellular superoxide dismutase (SOD3, ecSOD) contributes to the development of [[hypertension]].<ref name="pmid16864745">{{cite journal | vauthors = Gongora MC, Qin Z, Laude K, Kim HW, McCann L, Folz JR, Dikalov S, Fukai T, Harrison DG | display-authors = 6 | title = Role of extracellular superoxide dismutase in hypertension | journal = Hypertension | volume = 48 | issue = 3 | pages = 473–481 | date = September 2006 | pmid = 16864745 | doi = 10.1161/01.HYP.0000235682.47673.ab | doi-access = free }}</ref><ref name="pmid20008675">{{cite journal | vauthors = Lob HE, Marvar PJ, Guzik TJ, Sharma S, McCann LA, Weyand C, Gordon FJ, Harrison DG | display-authors = 6 | title = Induction of hypertension and peripheral inflammation by reduction of extracellular superoxide dismutase in the central nervous system | journal = Hypertension | volume = 55 | issue = 2 | pages = 277–83, 6p following 283 | date = February 2010 | pmid = 20008675 | pmc = 2813894 | doi = 10.1161/HYPERTENSIONAHA.109.142646 }}</ref> Inactivation of SOD2 in mice causes perinatal lethality.<ref name="pmid7493016"/>