WoS İndeksli Yayınlar Koleksiyonu / WoS Indexed Publications Collection

Permanent URI for this collectionhttps://hdl.handle.net/11147/7150

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Subject: search.filters.subject.NeuroinflammationWoS Q: search.filters.wosQuartile.Q2

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  • Article
    Role of Long Non-Coding RNA X-Inactive Transcript (XIST) in Neuroinflammation and Myelination: Insights From Cerebral Organoids and Implications for Multiple Sclerosis
    (MDPI, 2025) Pepe, Nihan Aktas; Acar, Busra; Zararsiz, Gozde Erturk; Guner, Serife Ayaz; Sen, Alaattin
    Background/Objectives: X-inactive-specific transcript (XIST) is a factor that plays a role in neuroinflammation. This study investigated the role of XIST in neuronal development, neuroinflammation, myelination, and therapeutic responses within cerebral organoids in the context of Multiple Sclerosis (MS) pathogenesis. Methods: Human cerebral organoids with oligodendrocytes were produced from XIST-silenced H9 cells, and the mature organoids were subsequently treated with either FTY720 or DMF. Gene expression related to inflammation and myelination was subsequently analyzed via qRT-PCR. Immunofluorescence staining was used to assess the expression of proteins related to inflammation, myelination, and neuronal differentiation. Alpha-synuclein protein levels were also checked via ELISA. Finally, transcriptome analysis was conducted on the organoid samples. Results: XIST-silenced organoids presented a 2-fold increase in the expression of neuronal stem cells, excitatory neurons, microglia, and mature oligodendrocyte markers. In addition, XIST silencing increased IL-10 mRNA expression by 2-fold and MBP and PLP1 expression by 2.3- and 0.6-fold, respectively. Although XIST silencing tripled IBA1 protein expression, it did not affect organoid MBP expression. FTY720, but not DMF, distinguished MBP and IBA1 expression in XIST-silenced organoids. Furthermore, XIST silencing reduced the concentration of alpha-synuclein from 300 to 100 pg/mL, confirming its anti-inflammatory role. Transcriptomic and gene enrichment analyses revealed that the differentially expressed genes are involved in neural development and immune processes, suggesting the role of XIST in neuroinflammation. The silencing of XIST modified the expression of genes associated with inflammation, myelination, and neuronal growth in cerebral organoids, indicating a potential involvement in the pathogenesis of MS. Conclusions: XIST may contribute to the MS pathogenesis as well as neuroinflammatory diseases such as and Alzheimer's and Parkinson's diseases and may be a promising therapeutic target.
  • Article
    Citation - WoS: 2
    Citation - Scopus: 2
    Combined Treatment of Ketogenic Diet and Propagermanium Reduces Neuroinflammation in Tay-Sachs Disease Mouse Model
    (Springer/Plenum Publishers, 2025) Inci, Orhan Kerim; Seyrantepe, Volkan
    Tay-Sachs disease is a rare lysosomal storage disorder caused by beta-Hexosaminidase A enzyme deficiency causing abnormal GM2 ganglioside accumulation in the central nervous system. GM2 accumulation triggers chronic neuroinflammation due to neurodegeneration-based astrogliosis and macrophage activity with the increased expression level of Ccl2 in the cortex of a recently generated Tay-Sachs disease mouse model Hexa-/-Neu3-/-. Propagermanium blocks the neuroinflammatory response induced by Ccl2, which is highly expressed in astrocytes and microglia. The ketogenic diet has broad potential usage in neurological disorders, but the knowledge of the impact on Tay-Sach disease is limited. This study aimed to display the effect of combining the ketogenic diet and propagermanium treatment on chronic neuroinflammation in the Tay-Sachs disease mouse model. Hexa-/-Neu3-/- mice were placed into the following groups: (i) standard diet, (ii) ketogenic diet, (iii) standard diet with propagermanium, and (iv) ketogenic diet with propagermanium. RT-PCR and immunohistochemistry analyzed neuroinflammation markers. Behavioral analyses were also applied to assess phenotypic improvement. Notably, the expression levels of neuroinflammation-related genes were reduced in the cortex of 140-day-old Hexa-/-Neu3-/- mice compared to beta-Hexosaminidase A deficient mice (Hexa-/-) after combined treatment. Immunohistochemical analysis displayed correlated results with the RT-PCR. Our data suggest the potential to implement combined treatment to reduce chronic inflammation in Tay-Sachs and other lysosomal storage diseases.