{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T00:32:57Z","timestamp":1774312377266,"version":"3.50.1"},"reference-count":97,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2023,4,12]],"date-time":"2023-04-12T00:00:00Z","timestamp":1681257600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006393","name":"University of Granada","doi-asserted-by":"publisher","award":["PPJIA2022.09"],"award-info":[{"award-number":["PPJIA2022.09"]}],"id":[{"id":"10.13039\/501100006393","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the progressive loss of motor neurons in the spinal cord, brain stem, and cerebral cortex. Biomarkers for ALS are essential for disease detection and to provide information on potential therapeutic targets. Aminopeptidases catalyze the cleavage of amino acids from the amino terminus of protein or substrates such as neuropeptides. Since certain aminopeptidases are known to increase the risk of neurodegeneration, such mechanisms may reveal new targets to determine their association with ALS risk and their interest as a diagnostic biomarker. The authors performed a systematic review and meta-analyses of genome-wide association studies (GWASs) to identify reported aminopeptidases genetic loci associated with the risk of ALS. PubMed, Scopus, CINAHL, ISI Web of Science, ProQuest, LILACS, and Cochrane databases were searched to retrieve eligible studies in English or Spanish, published up to 27 January 2023. A total of 16 studies were included in this systematic review, where a series of aminopeptidases could be related to ALS and could be promising biomarkers (DPP1, DPP2, DPP4, LeuAP, pGluAP, and PSA\/NPEPPS). The literature reported the association of single-nucleotide polymorphisms (SNPs: rs10260404 and rs17174381) with the risk of ALS. The genetic variation rs10260404 in the DPP6 gene was identified to be highly associated with ALS susceptibility, but meta-analyses of genotypes in five studies in a matched cohort of different ancestry (1873 cases and 1861 control subjects) showed no ALS risk association. Meta-analyses of eight studies for minor allele frequency (MAF) also found no ALS association for the \u201cC\u201d allele. The systematic review identified aminopeptidases as possible biomarkers. However, the meta-analyses for rs1060404 of DPP6 do not show a risk associated with ALS.<\/jats:p>","DOI":"10.3390\/ijms24087169","type":"journal-article","created":{"date-parts":[[2023,4,13]],"date-time":"2023-04-13T02:29:15Z","timestamp":1681352955000},"page":"7169","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Systematic Review and Meta-Analyses of Aminopeptidases as Prognostic Biomarkers in Amyotrophic Lateral Sclerosis"],"prefix":"10.3390","volume":"24","author":[{"given":"B\u00e1rbara","family":"Teruel-Pe\u00f1a","sequence":"first","affiliation":[{"name":"Department of Health Sciences, University of Ja\u00e9n, 23071 Ja\u00e9n, Spain"},{"name":"Department of Physiology, Faculty of Health Sciences, Ceuta University of Granada, 51001 Ceuta, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8684-1817","authenticated-orcid":false,"given":"Jos\u00e9 Lu\u00eds","family":"G\u00f3mez-Urquiza","sequence":"additional","affiliation":[{"name":"Nursing Department, Faculty of Health Sciences, Ceuta University of Granada, 51001 Ceuta, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4133-0092","authenticated-orcid":false,"given":"Nora","family":"Suleiman-Martos","sequence":"additional","affiliation":[{"name":"Nursing Department, Faculty of Health Sciences, University of Granada, 18071 Granada, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0624-9504","authenticated-orcid":false,"given":"Isabel","family":"Prieto","sequence":"additional","affiliation":[{"name":"Department of Health Sciences, University of Ja\u00e9n, 23071 Ja\u00e9n, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3720-259X","authenticated-orcid":false,"given":"Francisco Jos\u00e9","family":"Garc\u00eda-C\u00f3zar","sequence":"additional","affiliation":[{"name":"Department of Biomedicine, Biotechnology and Public Health, University of Cadiz, 11003 Cadiz, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manuel","family":"Ram\u00edrez-S\u00e1nchez","sequence":"additional","affiliation":[{"name":"Department of Health Sciences, University of Ja\u00e9n, 23071 Ja\u00e9n, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6387-4456","authenticated-orcid":false,"given":"Carmen","family":"Fern\u00e1ndez-Martos","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, University of San Pablo CEU, 28003 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9546-9148","authenticated-orcid":false,"given":"Germ\u00e1n","family":"Dom\u00ednguez-V\u00edas","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Health Sciences, Ceuta University of Granada, 51001 Ceuta, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1425","DOI":"10.1016\/S0140-6736(96)91680-3","article-title":"Dose-Ranging Study of Riluzole in Amyotrophic Lateral Sclerosis. 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