{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T01:25:49Z","timestamp":1788312349742,"version":"build-2803163510"},"reference-count":50,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2023,6,20]],"date-time":"2023-06-20T00:00:00Z","timestamp":1687219200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Science Technology and Innovation (MAARIFAH), King Abdulaziz City for Science and Technology, Kingdom of Saudi Arabia","award":["08-MED 510\u201302"],"award-info":[{"award-number":["08-MED 510\u201302"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brain Sciences"],"abstract":"<jats:p>Background: Autism spectrum disorder (ASD) encompasses a group of disorders characterized by difficulties with social interaction and repetitive behavior. The condition is supposed to originate from early shifts in brain development, while the underlying processes are unknown. Moreover, a considerable number of patients with ASD experience digestive difficulties. Metalloproteases (ADAMs) are a class of enzymes capable of cleaving membrane-bound proteins. Members of this family, ADAM17 and ADAM22, have the ability to cleave proteins like the pro-inflammatory cytokine TNF-\u03ac and glutamate synaptic molecules, which are both engaged in neuro-inflammation and glutamate excitotoxicity as crucial etiological mechanisms in ASD. ADAM17 and ADAM22 may also have a role in ASD microbiota\u2013gut\u2013brain axis connections by regulating immunological and inflammatory responses in the intestinal tract. Subjects and Methods: Using ELISA kits, the plasma levels of ADAM17 and ADAM22 were compared in 40 children with ASD and 40 typically developing children. All of the autistic participants\u2019 childhood autism rating scores (CARS), social responsiveness scales (SRS), and short sensory profiles (SSP) were evaluated as indicators of ASD severity.\u00a0Results: Our results showed that plasma levels of ADAM17 were significantly lower in ASD children than in control children, while ADAM22 demonstrated non-significantly lower levels. Our data also indicate that while ADAM17 correlates significantly with age, ADAM22 correlates significantly with CARS as a marker of ASD severity. Conclusions: Our interpreted data showed that alteration in ADAM17 and ADAM22 might be associated with glutamate excitotoxicity, neuroinflammation, and altered gut microbiota as etiological mechanisms of ASD and could be an indicator of the severity of the disorder.<\/jats:p>","DOI":"10.3390\/brainsci13060972","type":"journal-article","created":{"date-parts":[[2023,6,20]],"date-time":"2023-06-20T02:26:56Z","timestamp":1687228016000},"page":"972","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Exploring the Potential Role of ADAM 17 and ADAM 22 in the Etiology of Autism Spectrum Disorders"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7162-2419","authenticated-orcid":false,"given":"Sarah H.","family":"Al-Mazidi","sequence":"first","affiliation":[{"name":"Department of Physiology, Faculty of Medicine, Imam Mohammed Ibn Saud Islamic University, Riyadh 11432, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Afaf","family":"El-Ansary","sequence":"additional","affiliation":[{"name":"Autism Center, Lotus Holistic Alternative Medical Center, Abu Dhabi 110281, United Arab Emirates"},{"name":"Autism Research and Treatment Centre, King Saud University, Riyadh 11461, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amani","family":"Abualnaja","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Medicine, Imam Mohammed Ibn Saud Islamic University, Riyadh 11432, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6438-0853","authenticated-orcid":false,"given":"Abdullah","family":"AlZarroug","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Medicine, Imam Mohammed Ibn Saud Islamic University, Riyadh 11432, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Turki","family":"Alharbi","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Medicine, Imam Mohammed Ibn Saud Islamic University, Riyadh 11432, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laila Y.","family":"Al-Ayadhi","sequence":"additional","affiliation":[{"name":"Autism Research and Treatment Centre, King Saud University, Riyadh 11461, Saudi Arabia"},{"name":"Department of Physiology, Faculty of Medicine, King Saud University, Riyadh 11461, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,6,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Afif, I.Y., Farkhan, M., Kurdi, O., Maula, M.I., Ammarullah, M.I., Setiyana, B., Jamari, J., and Winarni, T.I. 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