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 beta. 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 beta, while IFN gamma 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.

Neuroinflammation and Oxidative Stress in Individuals Affected by DiGeorge Syndrome / Menghi, Michela; Micangeli, Ginevra; Tarani, Francesca; Putotto, Carolina; Pirro, FEDERICA ANNA; Mariani, Alessandro; Petrella, Carla; Pulvirenti, Federica; Cinicola, BIANCA LAURA; Colloridi, Fiorenza; Tarani, Luigi; Fiore, Marco. - In: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES. - ISSN 1422-0067. - 24:4(2023), p. 4242. [10.3390/ijms24044242]

Neuroinflammation and Oxidative Stress in Individuals Affected by DiGeorge Syndrome

Michela Menghi
Primo
;
Ginevra Micangeli
Secondo
;
Francesca Tarani;Carolina Putotto;Federica Pirro;Alessandro Mariani
Membro del Collaboration Group
;
Carla Petrella;Federica Pulvirenti;Bianca Cinicola;Fiorenza Colloridi;LUIGI TARANI
Penultimo
;
2023

Abstract

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 beta. 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 beta, while IFN gamma 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.
2023
10p; 22q11.2 region; Del 22; ROS; genetic disorder; inflammation; rare disease
01 Pubblicazione su rivista::01a Articolo in rivista
Neuroinflammation and Oxidative Stress in Individuals Affected by DiGeorge Syndrome / Menghi, Michela; Micangeli, Ginevra; Tarani, Francesca; Putotto, Carolina; Pirro, FEDERICA ANNA; Mariani, Alessandro; Petrella, Carla; Pulvirenti, Federica; Cinicola, BIANCA LAURA; Colloridi, Fiorenza; Tarani, Luigi; Fiore, Marco. - In: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES. - ISSN 1422-0067. - 24:4(2023), p. 4242. [10.3390/ijms24044242]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1679501
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