Exploring the Potential Role of ADAM 17 and ADAM 22 in the Etiology of Autism Spectrum Disorders
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 considerab...
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MDPI AG
2023-06-01
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| Online Access: | https://www.mdpi.com/2076-3425/13/6/972 |
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| author | Sarah H. Al-Mazidi Afaf El-Ansary Amani Abualnaja Abdullah AlZarroug Turki Alharbi Laila Y. Al-Ayadhi |
| author_facet | Sarah H. Al-Mazidi Afaf El-Ansary Amani Abualnaja Abdullah AlZarroug Turki Alharbi Laila Y. Al-Ayadhi |
| author_sort | Sarah H. Al-Mazidi |
| collection | DOAJ |
| description | 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-ά 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–gut–brain 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’ childhood autism rating scores (CARS), social responsiveness scales (SRS), and short sensory profiles (SSP) were evaluated as indicators of ASD severity. Results: 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. |
| first_indexed | 2024-03-11T02:41:09Z |
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| issn | 2076-3425 |
| language | English |
| last_indexed | 2024-03-11T02:41:09Z |
| publishDate | 2023-06-01 |
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| record_format | Article |
| series | Brain Sciences |
| spelling | doaj.art-cf0bfa218ed84846a54931e3b0a8e6232023-11-18T09:37:08ZengMDPI AGBrain Sciences2076-34252023-06-0113697210.3390/brainsci13060972Exploring the Potential Role of ADAM 17 and ADAM 22 in the Etiology of Autism Spectrum DisordersSarah H. Al-Mazidi0Afaf El-Ansary1Amani Abualnaja2Abdullah AlZarroug3Turki Alharbi4Laila Y. Al-Ayadhi5Department of Physiology, Faculty of Medicine, Imam Mohammed Ibn Saud Islamic University, Riyadh 11432, Saudi ArabiaAutism Center, Lotus Holistic Alternative Medical Center, Abu Dhabi 110281, United Arab EmiratesDepartment of Physiology, Faculty of Medicine, Imam Mohammed Ibn Saud Islamic University, Riyadh 11432, Saudi ArabiaDepartment of Physiology, Faculty of Medicine, Imam Mohammed Ibn Saud Islamic University, Riyadh 11432, Saudi ArabiaDepartment of Physiology, Faculty of Medicine, Imam Mohammed Ibn Saud Islamic University, Riyadh 11432, Saudi ArabiaAutism Research and Treatment Centre, King Saud University, Riyadh 11461, Saudi ArabiaBackground: 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-ά 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–gut–brain 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’ childhood autism rating scores (CARS), social responsiveness scales (SRS), and short sensory profiles (SSP) were evaluated as indicators of ASD severity. Results: 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.https://www.mdpi.com/2076-3425/13/6/972metalloproteasesADAM17ADAM22neuroinflammationglutamate excitotoxicitygut–brain axis |
| spellingShingle | Sarah H. Al-Mazidi Afaf El-Ansary Amani Abualnaja Abdullah AlZarroug Turki Alharbi Laila Y. Al-Ayadhi Exploring the Potential Role of ADAM 17 and ADAM 22 in the Etiology of Autism Spectrum Disorders Brain Sciences metalloproteases ADAM17 ADAM22 neuroinflammation glutamate excitotoxicity gut–brain axis |
| title | Exploring the Potential Role of ADAM 17 and ADAM 22 in the Etiology of Autism Spectrum Disorders |
| title_full | Exploring the Potential Role of ADAM 17 and ADAM 22 in the Etiology of Autism Spectrum Disorders |
| title_fullStr | Exploring the Potential Role of ADAM 17 and ADAM 22 in the Etiology of Autism Spectrum Disorders |
| title_full_unstemmed | Exploring the Potential Role of ADAM 17 and ADAM 22 in the Etiology of Autism Spectrum Disorders |
| title_short | Exploring the Potential Role of ADAM 17 and ADAM 22 in the Etiology of Autism Spectrum Disorders |
| title_sort | exploring the potential role of adam 17 and adam 22 in the etiology of autism spectrum disorders |
| topic | metalloproteases ADAM17 ADAM22 neuroinflammation glutamate excitotoxicity gut–brain axis |
| url | https://www.mdpi.com/2076-3425/13/6/972 |
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