Potential of GRID2 receptor gene for preventing TNF-induced neurodegeneration in autism
| Autor: | Belkis Atasever-Arslan, İlknur Melis Durasi, Zeynep Kalkan, Ugur Sezerman |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Candidate gene Apoptosis Tretinoin Epigenetics of autism 03 medical and health sciences 0302 clinical medicine Neural Stem Cells Cell Line Tumor medicine CACNA1H Humans Autistic Disorder cdc42 GTP-Binding Protein Genetic Association Studies Adaptor Proteins Signal Transducing Neurons Genetics biology Tumor Necrosis Factor-alpha General Neuroscience Neurodegeneration Glutamate receptor Computational Biology Golgi Matrix Proteins Membrane Proteins Membrane Transport Proteins Cell Differentiation medicine.disease 030104 developmental biology Receptors Glutamate Autism spectrum disorder Nerve Degeneration biology.protein Autism Carrier Proteins Neuroscience Biomarkers 030217 neurology & neurosurgery Signal Transduction GRID2 |
| Zdroj: | Neuroscience Letters. 620:62-69 |
| ISSN: | 0304-3940 |
| DOI: | 10.1016/j.neulet.2016.03.043 |
| Popis: | Autism is one of the most common subtypes of autism spectrum disorder (ASD). Recent studies suggested a relationship between immune-dependent coding genes and ASD, indicating that long term neuroimmunological anomalies affect brain development and synaptic transmission among neural networks. Furthermore, various studies focused on biomarker potential of TNF-α in autism. Ionotropic receptors are also studied as potential marker for autism since altered gene expression levels are observed in autistic patients. GRID2 is a candidate ionotropic receptor which is involved glutamate transfer. In this study, to propose TNF-α dependent cellular processes involved in autism aetiology in relation to GRID2 we performed a bioinformatic network analysis and identified potential pathways and genes that are involved in TNF-α induced changes at GRID2 receptor levels. As a result, we ascertained the GRID2 receptor gene as a candidate gene and further studied the association between GRID2 expression levels and TNF-induced neurodegeneration. Our bioinformatic analyses and experimental results revealed that TNF-α regulates GRID2 gene expression by activating Cdc42 and GOPC genes. Moreover, increased TNF-α levels leads to increase of caspase-3 protein levels triggering neuronal apoptosis leading to neuronal deficiency, which is one of the major symptoms of autism. The study is the first to show the role of TNF-α in regulation of GRID2 gene expression and its signalling pathway. As a result, GRID2 gene can be a suppressor in TNF-induced neurodegeneration which may help to understand the main factors leading to autism. |
| Databáze: | OpenAIRE |
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