Dysregulation of PINCH signaling in mesial temporal epilepsy

Charles Liu, Jon Russin, Christianne Heck, Keisuke Kawata, Radhika Adiga, William Yen, Jonathan Lambert, Benjamin Stear, Meng Law, Yvette Marquez, Peter Crino, David Millett, Dianne Langford

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7 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)43-52
Number of pages10
JournalJournal of Clinical Neuroscience
Volume36
DOIs
Publication statusPublished - 1 Feb 2017
Externally publishedYes

Keywords

  • Hippocampal sclerosis
  • Hyperphosphorylated Tau
  • Mesial temporal lobe epilepsy
  • PINCH protein

Cite this

Liu, C., Russin, J., Heck, C., Kawata, K., Adiga, R., Yen, W., Lambert, J., Stear, B., Law, M., Marquez, Y., Crino, P., Millett, D., & Langford, D. (2017). Dysregulation of PINCH signaling in mesial temporal epilepsy. Journal of Clinical Neuroscience, 36, 43-52. https://doi.org/10.1016/j.jocn.2016.10.012