Do Autism Spectrum and Autoimmune Disorders Share Predisposition Gene Signature Due to mTOR Signaling Pathway Controlling Expression?

Trifonova, E. A.; Klimenko, Alexandra I.; Мустафин, З. С.; Lashin, Sergey A.; Кочетов, А. В.

doi:10.3390/ijms22105248

Cited by 9 publications

(7 citation statements)

References 51 publications

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“…We have bioinformatically demonstrated that autism spectrum and autoimmune disorders do share predisposition gene signatures due to mTOR signaling pathway controlling expression. Our network analysis revealed that the great majority (up to 67%) of AID genes are related to the mTOR signaling pathway directly or indirectly [67]. Our bioinformatic analysis and reviewed published data allow us to hypothesize that both a certain part of ASD and AID comprise a connected set of disorders sharing a common aberrant pathway (mTOR signaling) rather than a vast set of different disorders.…”

Section: Mtor Signaling As a Key Player In Immune Microbiome And Beha...mentioning

confidence: 78%

“…Our bioinformatic analysis and reviewed published data allow us to hypothesize that both a certain part of ASD and AID comprise a connected set of disorders sharing a common aberrant pathway (mTOR signaling) rather than a vast set of different disorders. Furthermore, a certain part of the autism spectrum might be a specific type of autoimmune disorder with an early manifestation of a unique set of predominantly behavioral symptoms [67].…”

Section: Mtor Signaling As a Key Player In Immune Microbiome And Beha...mentioning

confidence: 99%

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Abnormal mTOR Activity in Pediatric Autoimmune Neuropsychiatric and MIA-Associated Autism Spectrum Disorders

Trifonova

Мустафин

Lashin

et al. 2022

IJMS

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Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by the early onset of communication and behavioral problems. ASD is highly heritable; however, environmental factors also play a considerable role in this disorder. A significant part of both syndromic and idiopathic autism cases could be attributed to disorders caused by mammalian target of rapamycin (mTOR)-dependent translation deregulation. This narrative review analyzes both bioinformatic and experimental evidence that connects mTOR signaling to the maternal autoantibody-related (MAR) autism spectrum and autoimmune neuropsychiatric disorders simultaneously. In addition, we reconstruct a network presenting the interactions between the mTOR signaling and eight MAR ASD genes coding for ASD-specific maternal autoantibody target proteins. The research discussed in this review demonstrates novel perspectives and validates the need for a subtyping of ASD on the grounds of pathogenic mechanisms. The utter necessity of designing ELISA-based test panels to identify all antibodies related to autism-like behavior is also considered.

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Section: Mtor Signaling As a Key Player In Immune Microbiome And Beha...mentioning

confidence: 78%

Section: Mtor Signaling As a Key Player In Immune Microbiome And Beha...mentioning

confidence: 99%

Abnormal mTOR Activity in Pediatric Autoimmune Neuropsychiatric and MIA-Associated Autism Spectrum Disorders

Trifonova

Мустафин

Lashin

et al. 2022

IJMS

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“…Hence, Trifonova et al. proposed more attention should be paid on the mTOR signaling pathway for ASD investigation ( 22 , 43 ). Our results thereby strongly support this notion.…”

Section: Discussionmentioning

confidence: 99%

mTOR Signaling Pathway Regulates the Release of Proinflammatory Molecule CCL5 Implicated in the Pathogenesis of Autism Spectrum Disorder

Wang

Qin

et al. 2022

Front. Immunol.

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Autism spectrum disorder (ASD) is a complex pervasive neurodevelopmental disorder and neuroinflammation may contribute to the pathogenesis of ASD. However, the exact mechanisms of abnormal release of proinflammatory mediators in ASD remain poorly understood. This study reports elevated plasma levels of the proinflammatory chemokine (C-C motif) ligand 5 (CCL5) in children with ASD, suggesting an aberrant inflammatory response appearing in the development of ASD. Mining of the expression data of brain or blood tissue from individuals with ASD reveals that mTOR signaling is aberrantly activated in ASD patients. Our in vitro study shows that suppression of mTOR reduces the gene expression and release of CCL5 from human microglia, supporting that CCL5 expression is regulated by mTOR activity. Furthermore, bacterial lipopolysaccharide (LPS)-induced CCL5 expression can be counteracted by siRNA against NF-κB, suggests a determining role of NF-κB in upregulating CCL5 expression. However, a direct regulatory relationship between the NF-κB element and the mTOR signaling pathway was not observed in rapamycin-treated cells. Our results show that the phosphorylated CREB can be induced to suppress CCL5 expression by outcompeting NF-κB in binding to CREB-binding protein (CREBBP) once the mTOR signaling pathway is inhibited. We propose that the activation of mTOR signaling in ASD may induce the suppression of phosphorylation of CREB, which in turn results in the increased binding of CREBBP to NF-κB, a competitor of phosphorylated CREB to drive expression of CCL5. Our study sheds new light on the inflammatory mechanisms of ASD and paves the way for the development of therapeutic strategy for ASD.

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“…Gene network modeling was applied to study aggressive behavior pattern based on associative network reconstruction [34] using ANDSystem (Associative Network Discovery System), a tool for the automatic extraction of knowledge from scientific publications [35]. Ekaterina Trifonova and co-authors used gene network reconstruction to analyze role of mTOR signaling pathway in autism spectrum disorder (ASD) [36,37]. ASD is characterized by high genetic heterogeneity, as well as autoimmune disorders.…”

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confidence: 99%

Recent Trends in Cancer Genomics and Bioinformatics Tools Development

Anashkina

Leberfarb

Orlov

2021

IJMS

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Do Autism Spectrum and Autoimmune Disorders Share Predisposition Gene Signature Due to mTOR Signaling Pathway Controlling Expression?

Cited by 9 publications

References 51 publications

Abnormal mTOR Activity in Pediatric Autoimmune Neuropsychiatric and MIA-Associated Autism Spectrum Disorders

Abnormal mTOR Activity in Pediatric Autoimmune Neuropsychiatric and MIA-Associated Autism Spectrum Disorders

mTOR Signaling Pathway Regulates the Release of Proinflammatory Molecule CCL5 Implicated in the Pathogenesis of Autism Spectrum Disorder

Recent Trends in Cancer Genomics and Bioinformatics Tools Development

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