Downregulation of DDIT4 ameliorates abnormal behaviors in autism by inhibiting ferroptosis via the PI3K/Akt pathway

Luo, Ting; Chen, Sisi; Ruan, Yijun; Chen, Huaying; Chen, Yumei; Li, Yamin; Zhou, Wen

doi:10.1016/j.bbrc.2022.12.032

Cited by 9 publications

(2 citation statements)

References 27 publications

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“…The DNA Damage Inducible Transcript 4 (DDIT4) gene linked to both GOCC_ mitochondrion and GOBP_Response_To_Oxygen_Containing_Compound. Luo et al (2023) [59] found that DDIT4 expression appears to be involved in ferroptosis in subjects with ASD. DDIT4 gene protein expression is associated with stress responses such as hypoxia, energetic stress, DNA damage, nutrient depletion, and endoplasmic reticulum stress [59].…”

Section: Gocc_mitochondrionmentioning

confidence: 99%

“…Luo et al (2023) [59] found that DDIT4 expression appears to be involved in ferroptosis in subjects with ASD. DDIT4 gene protein expression is associated with stress responses such as hypoxia, energetic stress, DNA damage, nutrient depletion, and endoplasmic reticulum stress [59]. Overexpression of DDIT4 can inactivate the PI3K/Akt pathway and promote neuronal ferroptosis, contributing to the onset of autism symptoms [59].…”

Section: Gocc_mitochondrionmentioning

confidence: 99%

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Transcriptome Study in Sicilian Patients with Autism Spectrum Disorder

Salemi,

Schillaci,

Lanza

et al. 2024

Biomedicines

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ASD is a complex condition primarily rooted in genetics, although influenced by environmental, prenatal, and perinatal risk factors, ultimately leading to genetic and epigenetic alterations. These mechanisms may manifest as inflammatory, oxidative stress, hypoxic, or ischemic damage. To elucidate potential variances in gene expression in ASD, a transcriptome analysis of peripheral blood mononuclear cells was conducted via RNA-seq on 12 ASD patients and 13 healthy controls, all of Sicilian ancestry to minimize environmental confounds. A total of 733 different statistically significant genes were identified between the two cohorts. Gene Set Enrichment Analysis (GSEA) and Gene Ontology (GO) terms were employed to explore the pathways influenced by differentially expressed mRNAs. GSEA revealed GO pathways strongly associated with ASD, namely the GO Biological Process term “Response to Oxygen-Containing Compound”. Additionally, the GO Cellular Component pathway “Mitochondrion” stood out among other pathways, with differentially expressed genes predominantly affiliated with this specific pathway, implicating the involvement of different mitochondrial functions in ASD. Among the differentially expressed genes, FPR2 was particularly highlighted, belonging to three GO pathways. FPR2 can modulate pro-inflammatory responses, with its intracellular cascades triggering the activation of several kinases, thus suggesting its potential utility as a biomarker of pro-inflammatory processes in ASD.

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Section: Gocc_mitochondrionmentioning

confidence: 99%