{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,7,20]],"date-time":"2024-07-20T12:12:03Z","timestamp":1721477523509},"reference-count":38,"publisher":"Walter de Gruyter GmbH","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,6,26]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec id=\"j_dmpt-2018-0038_s_999\"><jats:title id=\"d2980143e5301\">Background<\/jats:title><jats:p>The S-oxidation of S-carboxymethyl-L-cysteine has been reported previously to be a biomarker of disease susceptibility in Parkinson\u2019s disease and amyotrophic lateral sclerosis. In the present investigation, the original observations have been extended and confirmed.<\/jats:p><\/jats:sec><jats:sec id=\"j_dmpt-2018-0038_s_998\"><jats:title id=\"d2980143e5310\">Methods<\/jats:title><jats:p>Meta-analysis of previously published investigations into the S-oxidation polymorphism together with new subject data was evaluated.<\/jats:p><\/jats:sec><jats:sec id=\"j_dmpt-2018-0038_s_997\"><jats:title id=\"d2980143e5319\">Results<\/jats:title><jats:p>The incidence of the poor metaboliser phenotype (no urinary recovery of S-oxide metabolites) was found to be 3%\u20137% within healthy and non-neurological disease populations, whereas 38% of the Parkinson\u2019s disease subjects and 39% of the amyotrophic lateral sclerosis group were phenotyped as poor metabolisers. The consequent odds risk ratio of developing Parkinson\u2019s disease was calculated to be 33.8 [95% confidence interval (CI), 13.3\u201386.1] and for amyotrophic lateral sclerosis was 35.2 (95% CI, 13.0\u201385.1).<\/jats:p><\/jats:sec><jats:sec id=\"j_dmpt-2018-0038_s_996\"><jats:title id=\"d2980143e5328\">Conclusions<\/jats:title><jats:p>The possible involvement of the enzyme responsible for this S-oxidation biotransformation reaction, phenylalanine hydroxylase, should be further investigated to elucidate its potential role in the mechanism(s) of toxicity in susceptible individuals displaying these diseases. The \u201cJanus hypothesis,\u201d possibly explaining why phenylalanine hydroxylase is a biomarker of neurodegenerative disease susceptibility, together with the general theme that this concept may apply to many other hitherto unsuspected enzyme systems, is presented.<\/jats:p><\/jats:sec>","DOI":"10.1515\/dmpt-2018-0038","type":"journal-article","created":{"date-parts":[[2019,6,29]],"date-time":"2019-06-29T09:06:16Z","timestamp":1561799176000},"source":"Crossref","is-referenced-by-count":2,"title":["Drug S-oxidation and phenylalanine hydroxylase: a biomarker for neurodegenerative susceptibility in Parkinson\u2019s disease and amyotrophic lateral sclerosis"],"prefix":"10.1515","volume":"34","author":[{"given":"Lucinda","family":"Rawlings","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"Turton","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephen C.","family":"Mitchell","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Glyn B.","family":"Steventon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"374","reference":[{"key":"ref71","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1111\/j.1365-2125.1984.tb02498.x","article-title":"Genetic aspects of the polymodally distributed sulphoxidation of S-carboxymethyl-L-cysteine in man","volume":"18","year":"1984","journal-title":"Br J Clin Pharmacol"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"896","DOI":"10.1016\/S0140-6736(14)61393-3","article-title":"Parkinson\u2019s disease","volume":"386","year":"2015","journal-title":"Lancet"},{"key":"ref201","doi-asserted-by":"crossref","first-page":"896","DOI":"10.1016\/S0140-6736(14)61393-3","article-title":"Parkinson\u2019s disease","volume":"386","year":"2015","journal-title":"Lancet"},{"key":"ref231","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1136\/jnnp.53.7.621-a","article-title":"Pesticide toxicity and motor neurone disease","volume":"53","year":"1990","journal-title":"J Neurol Neurosurg Psychiat"},{"key":"ref301","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1515\/DMDI.2004.20.3.159","article-title":"Mitchell SC, Steventon GB. 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