Neuroinflammation and Oxidative Stress in Individuals Affected by DiGeorge Syndrome
DiGeorge syndrome (DGS) is a rare genetic disease caused by microdeletions of the 22q11.2 region (DGS1). A haploinsufficiency at 10p level has been proposed also as a DGS cause (DGS2). Clinical manifestations are variable. The most frequent features are thymic hypoplasia or aplasia with consequent i...
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MDPI AG
2023-02-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/4/4242 |
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| author | Michela Menghi Ginevra Micangeli Francesca Tarani Carolina Putotto Federica Pirro Alessandro Mariani Carla Petrella Federica Pulvirenti Bianca Cinicola Fiorenza Colloridi Luigi Tarani Marco Fiore |
| author_facet | Michela Menghi Ginevra Micangeli Francesca Tarani Carolina Putotto Federica Pirro Alessandro Mariani Carla Petrella Federica Pulvirenti Bianca Cinicola Fiorenza Colloridi Luigi Tarani Marco Fiore |
| author_sort | Michela Menghi |
| collection | DOAJ |
| description | DiGeorge syndrome (DGS) is a rare genetic disease caused by microdeletions of the 22q11.2 region (DGS1). A haploinsufficiency at 10p level has been proposed also as a DGS cause (DGS2). Clinical manifestations are variable. The most frequent features are thymic hypoplasia or aplasia with consequent immune deficiency, cardiac malformations, hypoparathyroidism, facial and palatine abnormalities, variable degrees of cognitive impairment and psychiatric disorders. The specific aim of this descriptive report is to discuss the correlation between oxidative stress and neuroinflammation in DGS patients with microdeletions of the 22q11.2 region. The deleted chromosomic region maps various genes involved in mitochondrial metabolisms, such as DGCR8 and TXNRD2, that could lead to reactive oxygen species (ROS) increased production and antioxidant depletion. Furthermore, increased levels of ROS in mitochondria would lead to the destruction of the projection neurons in the cerebral cortex with consequent neurocognitive impairment. Finally, the increase in modified protein belonging to the family of sulfoxide compounds and hexoses, acting as inhibitors of the IV and V mitochondria complex, could result in direct ROS overproduction. Neuroinflammation in DGS individuals could be directly related to the development of the syndrome’s characteristic psychiatric and cognitive disorders. In patients with psychotic disorders, the most frequent psychiatric manifestation in DGS, Th-17, Th-1 and Th-2 cells are increased with consequent elevation of proinflammatory cytokine IL-6 and IL1<inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mi mathvariant="sans-serif">β</mi></semantics></math></inline-formula>. In patients with anxiety disorders, both CD3 and CD4 are increased. Some patients with autism spectrum disorders (ASDs) have an augmented level of proinflammatory cytokines IL-12, IL-6 and IL-1<inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mi mathvariant="sans-serif">β</mi></semantics></math></inline-formula>, while IFN<inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mi mathvariant="sans-serif">γ</mi></semantics></math></inline-formula> and the anti-inflammatory cytokine IL-10 seem to be reduced. Other data proposed that altered synaptic plasticity could be directly involved in DGS cognitive disorders. In conclusion, the use of antioxidants for restoring mitochondrial functionality in DGS could be a useful tool to protect cortical connectivity and cognitive behavior. |
| first_indexed | 2024-03-11T08:39:26Z |
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| spelling | doaj.art-2481ad1b93aa46928191758f7a0faf832023-11-16T21:11:33ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-02-01244424210.3390/ijms24044242Neuroinflammation and Oxidative Stress in Individuals Affected by DiGeorge SyndromeMichela Menghi0Ginevra Micangeli1Francesca Tarani2Carolina Putotto3Federica Pirro4Alessandro Mariani5Carla Petrella6Federica Pulvirenti7Bianca Cinicola8Fiorenza Colloridi9Luigi Tarani10Marco Fiore11Department of Maternal Infantile and Urological Sciences, Sapienza University of Rome, 00185 Rome, Italy Department of Maternal Infantile and Urological Sciences, Sapienza University of Rome, 00185 Rome, Italy Department of Maternal Infantile and Urological Sciences, Sapienza University of Rome, 00185 Rome, Italy Department of Maternal Infantile and Urological Sciences, Sapienza University of Rome, 00185 Rome, Italy Department of Maternal Infantile and Urological Sciences, Sapienza University of Rome, 00185 Rome, Italy Department of Internal, Anesthesiologic and Cardiovascular Clinical Sciences, Sapienza University of Rome, 00185 Rome, ItalyRegional Reference Centre for Primary Immune Deficiencies, Azienda Ospedaliera Universitaria Policlinico Umberto I, 00185 Rome, ItalyRegional Reference Centre for Primary Immune Deficiencies, Azienda Ospedaliera Universitaria Policlinico Umberto I, 00185 Rome, ItalyDepartment of Maternal Infantile and Urological Sciences, Sapienza University of Rome, 00185 Rome, Italy Department of Maternal Infantile and Urological Sciences, Sapienza University of Rome, 00185 Rome, Italy Department of Maternal Infantile and Urological Sciences, Sapienza University of Rome, 00185 Rome, Italy Regional Reference Centre for Primary Immune Deficiencies, Azienda Ospedaliera Universitaria Policlinico Umberto I, 00185 Rome, ItalyDiGeorge syndrome (DGS) is a rare genetic disease caused by microdeletions of the 22q11.2 region (DGS1). A haploinsufficiency at 10p level has been proposed also as a DGS cause (DGS2). Clinical manifestations are variable. The most frequent features are thymic hypoplasia or aplasia with consequent immune deficiency, cardiac malformations, hypoparathyroidism, facial and palatine abnormalities, variable degrees of cognitive impairment and psychiatric disorders. The specific aim of this descriptive report is to discuss the correlation between oxidative stress and neuroinflammation in DGS patients with microdeletions of the 22q11.2 region. The deleted chromosomic region maps various genes involved in mitochondrial metabolisms, such as DGCR8 and TXNRD2, that could lead to reactive oxygen species (ROS) increased production and antioxidant depletion. Furthermore, increased levels of ROS in mitochondria would lead to the destruction of the projection neurons in the cerebral cortex with consequent neurocognitive impairment. Finally, the increase in modified protein belonging to the family of sulfoxide compounds and hexoses, acting as inhibitors of the IV and V mitochondria complex, could result in direct ROS overproduction. Neuroinflammation in DGS individuals could be directly related to the development of the syndrome’s characteristic psychiatric and cognitive disorders. In patients with psychotic disorders, the most frequent psychiatric manifestation in DGS, Th-17, Th-1 and Th-2 cells are increased with consequent elevation of proinflammatory cytokine IL-6 and IL1<inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mi mathvariant="sans-serif">β</mi></semantics></math></inline-formula>. In patients with anxiety disorders, both CD3 and CD4 are increased. Some patients with autism spectrum disorders (ASDs) have an augmented level of proinflammatory cytokines IL-12, IL-6 and IL-1<inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mi mathvariant="sans-serif">β</mi></semantics></math></inline-formula>, while IFN<inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mi mathvariant="sans-serif">γ</mi></semantics></math></inline-formula> and the anti-inflammatory cytokine IL-10 seem to be reduced. Other data proposed that altered synaptic plasticity could be directly involved in DGS cognitive disorders. In conclusion, the use of antioxidants for restoring mitochondrial functionality in DGS could be a useful tool to protect cortical connectivity and cognitive behavior.https://www.mdpi.com/1422-0067/24/4/4242ROSrare diseaseDel 22genetic disorderinflammation22q11.2 region |
| spellingShingle | Michela Menghi Ginevra Micangeli Francesca Tarani Carolina Putotto Federica Pirro Alessandro Mariani Carla Petrella Federica Pulvirenti Bianca Cinicola Fiorenza Colloridi Luigi Tarani Marco Fiore Neuroinflammation and Oxidative Stress in Individuals Affected by DiGeorge Syndrome International Journal of Molecular Sciences ROS rare disease Del 22 genetic disorder inflammation 22q11.2 region |
| title | Neuroinflammation and Oxidative Stress in Individuals Affected by DiGeorge Syndrome |
| title_full | Neuroinflammation and Oxidative Stress in Individuals Affected by DiGeorge Syndrome |
| title_fullStr | Neuroinflammation and Oxidative Stress in Individuals Affected by DiGeorge Syndrome |
| title_full_unstemmed | Neuroinflammation and Oxidative Stress in Individuals Affected by DiGeorge Syndrome |
| title_short | Neuroinflammation and Oxidative Stress in Individuals Affected by DiGeorge Syndrome |
| title_sort | neuroinflammation and oxidative stress in individuals affected by digeorge syndrome |
| topic | ROS rare disease Del 22 genetic disorder inflammation 22q11.2 region |
| url | https://www.mdpi.com/1422-0067/24/4/4242 |
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