2. Academic Validation
  3. Suppression of AKAP150 palmitoylation alleviates seizures in kainic acid-induced epilepsy mice

Suppression of AKAP150 palmitoylation alleviates seizures in kainic acid-induced epilepsy mice

  • Neuroscience. 2025 Dec 5:590:83-92. doi: 10.1016/j.neuroscience.2025.10.061.
Chen-Chao Chu 1,  Ya-Hui Hu 2,  Hai-Feng Zhang 1,  Gui-Zhou Li 3,  Shi-Yu Wu 1,  Yan-Yu Zang 4,  Jiang Chen 5,  Hao-Yu Wang 2,  Yang-Yang Xu 2,  Hong-Li Guo 6,  Yun Stone Shi 7,  Feng Chen 8
Affiliations

Affiliations

  • 1 Pharmaceutical Sciences Research Center, Department of Pharmacy, Children's Hospital of Nanjing Medical University, Nanjing, China; School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, China.
  • 2 Pharmaceutical Sciences Research Center, Department of Pharmacy, Children's Hospital of Nanjing Medical University, Nanjing, China.
  • 3 Pharmaceutical Sciences Research Center, Department of Pharmacy, Children's Hospital of Nanjing Medical University, Nanjing, China; Ministry of Education Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Jiangsu Key Laboratory of Molecular Medicine, Medical School, Nanjing University, Nanjing, China.
  • 4 Ministry of Education Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Jiangsu Key Laboratory of Molecular Medicine, Medical School, Nanjing University, Nanjing, China.
  • 5 Department of Neurology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China.
  • 6 Pharmaceutical Sciences Research Center, Department of Pharmacy, Children's Hospital of Nanjing Medical University, Nanjing, China. Electronic address: [email protected].
  • 7 Ministry of Education Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Jiangsu Key Laboratory of Molecular Medicine, Medical School, Nanjing University, Nanjing, China. Electronic address: [email protected].
  • 8 Pharmaceutical Sciences Research Center, Department of Pharmacy, Children's Hospital of Nanjing Medical University, Nanjing, China. Electronic address: [email protected].
PMID: 41187801 DOI: 10.1016/j.neuroscience.2025.10.061
Abstract

Epilepsy is a chronic and refractory neurological disorder, with drug resistance remaining a major challenge. Identifying new therapeutic targets could facilitate the development of more effective anti-seizure medications. AKAP79/150, a member of A-Kinase Anchoring Proteins (AKAPs) family, plays a critical role in synaptic transmission and plasticity. Although its implication in early epileptogenesis has been reported, its role in epilepsy progression remains unclear. In this study, using a kainic acid (KA)-induced epilepsy mouse model, we found that the expression and palmitoylation of AKAP150 in the hippocampus were significantly upregulated during epilepsy development. Silencing AKAP150 by the right intracerebroventricular (ICV) siRNA injections or inhibiting its palmitoylation by 2-bromohexadecanoic acid attenuated KA-induced epilepsy, as evidenced by reduced seizure severity, duration, and frequency of spontaneous recurrent seizures within 14 days. Mechanistically, AKAP79/150 interacts with protein kinase C (PKC) to suppress KCNQ expression, thereby diminishing inhibitory M-currents and contributing to epileptogenesis. Our findings reveal the pivotal role of AKAP79/150 in epilepsy progression and highlight its potential as a therapeutic target for epilepsy intervention.

Keywords

2-bromohexadecanoic acid; AKAP79/150; Epilepsy; Kainic acid; Palmitoylation; Protein kinase C.

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