{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T15:28:00Z","timestamp":1791559680974,"version":"4.3.4"},"reference-count":61,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2015,9,17]],"date-time":"2015-09-17T00:00:00Z","timestamp":1442448000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Fundamemntal Clinical Pharma"],"published-print":{"date-parts":[[2015,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Homocysteine (Hcy) is a nonproteogenic sulfur containing amino acid derived from dietary methionine through demethylation. Homocysteine can be re\u2010methylated to methionine [precursor of S\u2010adenosylmethionine (\n                    <jats:styled-content style=\"fixed-case\">SAM<\/jats:styled-content>\n                    )] via the re\u2010methylation or 5\u2010methyltetrahydrofolate pathway or undergoes transsulfuration to form cysteine by the action of metabolic enzymes and cofactors. Impaired metabolism due to genetic alteration in metabolic enzymes (methionine synthase, methyltetrahydrofolate reductase (\n                    <jats:styled-content style=\"fixed-case\">MTHFR<\/jats:styled-content>\n                    ), cystathionine \u03b2\u2010synthase (C\u03b2S), and cystathionine\u2010\u03b3\u2010lyase (C\u03b3L) or deficiency in cofactors (vitamin B\n                    <jats:sub>6<\/jats:sub>\n                    , B\n                    <jats:sub>12<\/jats:sub>\n                    , folate) may lead to acquired metabolic anomaly known as hyperhomocysteinemia. Hcy excess decreases the S\u2010adenosylmethionine (\n                    <jats:styled-content style=\"fixed-case\">SAM<\/jats:styled-content>\n                    )\u2010dependent synthesis of catecholamines, viz. dopamine, norepinephrine, epinephrine, and noncatecholamine, viz. serotonin (5\u2010\n                    <jats:styled-content style=\"fixed-case\">HT<\/jats:styled-content>\n                    ), due to genetic alteration in key enzyme\n                    <jats:styled-content style=\"fixed-case\">MTHFR<\/jats:styled-content>\n                    in the homocysteine metabolism pathway that leads to depression. Thus, hyperhomocysteinemia (\n                    <jats:styled-content style=\"fixed-case\">HH<\/jats:styled-content>\n                    cy)\u2010induced\n                    <jats:styled-content style=\"fixed-case\">SAM<\/jats:styled-content>\n                    level is influenced by the single nucleotide polymorphism (\n                    <jats:styled-content style=\"fixed-case\">SNP<\/jats:styled-content>\n                    )\n                    <jats:styled-content style=\"fixed-case\">MTHFR<\/jats:styled-content>\n                    C677T. Furthermore,\n                    <jats:styled-content style=\"fixed-case\">HH<\/jats:styled-content>\n                    cy leads to production of precarious neurotoxic product homocysteic acid (\n                    <jats:styled-content style=\"fixed-case\">HCA<\/jats:styled-content>\n                    ) and cysteine sulfinic acid (\n                    <jats:styled-content style=\"fixed-case\">CSA<\/jats:styled-content>\n                    ) which acts as an N\u2010methyl\u2010D\u2010aspartate (\n                    <jats:styled-content style=\"fixed-case\">NMDA<\/jats:styled-content>\n                    ) receptor agonist and has neurotoxic effects on dopaminergic neurons. In the current review, an attempt has been made to discuss the neurotoxic effects of\n                    <jats:styled-content style=\"fixed-case\">HH<\/jats:styled-content>\n                    cy in the pathogenesis of depression.\n                  <\/jats:p>","DOI":"10.1111\/fcp.12145","type":"journal-article","created":{"date-parts":[[2015,8,27]],"date-time":"2015-08-27T06:19:32Z","timestamp":1440656372000},"page":"522-528","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":140,"title":["Homocysteine excess: delineating the possible mechanism of neurotoxicity and depression"],"prefix":"10.1111","volume":"29","author":[{"given":"Pankaj","family":"Bhatia","sequence":"first","affiliation":[{"name":"CNS Research Laboratory Pharmacology Division Department of Pharmaceutical Sciences and Drug Research Faculty of Medicine Punjabi university Patiala 147002 Punjab India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nirmal","family":"Singh","sequence":"additional","affiliation":[{"name":"Pharmacology Division Department of Pharmaceutical Sciences and Drug Research Faculty of Medicine Punjabi university Patiala 147002 Punjab India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,9,17]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.2174\/1874241601104010034"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1176\/ajp.2007.164.6.861"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1586\/ern.09.75"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.109.130427"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/alcalc\/35.4.351"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2006.04.088"},{"key":"e_1_2_8_8_1","first-page":"25","article-title":"Elevated plasma homocysteine in association with decreased vitamin B12, folate, serotonin, lipids and lipoproteins in depressed patients","volume":"15","author":"Ebesunun M.O.","year":"2012","journal-title":"Afr. 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