Dysregulation of PINCH signaling in mesial temporal epilepsy
| Autor: | Dianne Langford, Yvette Marquez, Charles Y. Liu, David Millett, Benjamin Stear, Keisuke Kawata, Radhika Adiga, Jon Russin, Jonathan P. Lambert, Christianne N. Heck, Peter B. Crino, Meng Law, William Yen |
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| Rok vydání: | 2017 |
| Předmět: |
Adult
Male 0301 basic medicine Pathology medicine.medical_specialty tau Proteins Inflammation Hippocampal formation Hippocampus Epileptogenesis Article 03 medical and health sciences Epilepsy 0302 clinical medicine Physiology (medical) medicine Humans Protein kinase B Adaptor Proteins Signal Transducing Neurons Hippocampal sclerosis Glycogen Synthase Kinase 3 beta Kinase business.industry Membrane Proteins General Medicine LIM Domain Proteins Middle Aged medicine.disease nervous system diseases body regions 030104 developmental biology Epilepsy Temporal Lobe Neurology Astrocytes Case-Control Studies Phosphorylation Female Surgery Neurology (clinical) medicine.symptom business Proto-Oncogene Proteins c-akt Neuroscience 030217 neurology & neurosurgery Signal Transduction |
| Zdroj: | Journal of Clinical Neuroscience. 36:43-52 |
| ISSN: | 0967-5868 |
| Popis: | Mounting evidence suggests that inflammation is important in epileptogenesis. Particularly Interesting New Cysteine Histidine-rich (PINCH) protein is a highly conserved, LIM-domain protein known to interact with hyperphosphorylated Tau. We assessed PINCH expression in resected epileptogenic human hippocampi and further explored the relationships among PINCH, hpTau and associated kinases. Resected hippocampal tissue from 7 patients with mesial temporal lobe epilepsy (MTLE) was assessed by Western analyses to measure levels of PINCH and hyperphosphorylated Tau, as well as changes in phosphorylation levels of associated kinases AKT and GSK3β in comparison to normal control tissue. Immunolabeling was also conducted to evaluate PINCH and hpTau patterns of expression, co-localization and cell-type specific expression. Hippocampal PINCH was increased by 2.6 fold in the epilepsy cases over controls and hpTau was increased 10 fold over control. Decreased phospho-AKT and phospho-GSK3β in epilepsy tissue suggested involvement of this pathway in MTLE. PINCH and hpTau co-localized in some neurons in MTLE tissue. While PINCH was expressed by both neurons and astrocytes in MTLE tissue, hpTau was extracellular or associated with neurons. PINCH was absent from the serum of control subjects but readily detectable from the serum of patients with chronic epilepsy. Our study describes the expression of PINCH and points to AKT/GSK3β signaling dysregulation as a possible pathway in hpTau formation in MTLE. In view of the interactions between hpTau and PINCH, understanding the role of PINCH in MTLE may provide increased understanding of mechanisms leading to inflammation and MTLE epileptogenesis and a potential biomarker for drug-resistant epilepsy. |
| Databáze: | OpenAIRE |
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