MCC-135 Exerts Antiepileptic and Neuroprotective Effects by Downregulating NCX1 Expression to Decrease Intracellular Calcium Overload in the Hippocampus.
Overview
Abstract
Background: Approximately 30% of epilepsy patients still develop drug resistance after standard antiepileptic treatment. Therefore, there is an urgent need to identify new drug targets to improve seizure control. Previous studies have shown that NCX1 can regulate the intracellular Ca2+ levels in astrocytes and neurons, which are closely associated with epilepsy. MCC‐135 has shown potential as an antiseizure medication due to its ability to downregulate NCX and reduce intracellular calcium overload; however, its role and mechanism in epilepsy remain unclear.
Methods: This study employed single‐cell analysis and molecular docking to identify the potential molecular targets of MCC‐135 in treating epilepsy. Additionally, we used a KA‐induced epileptic mouse model to validate these molecular levels and the therapeutic effects and mechanisms of MCC‐135.
Results: Relative to controls, NCX1 expression was significantly upregulated in the hippocampus of KA‐induced epileptic mice. Immunofluorescence staining revealed that NCX1 was co‐localized with both astrocytes and neurons. MCC‐135 treatment significantly prolonged the seizure latency in KA‐induced epileptic mice and alleviated hippocampal neuronal damage. Furthermore, MCC‐135 effectively reduced NCX1 expression, alleviated intracellular calcium overload, and downregulated glutamate levels in the epileptic mice.
Conclusion: MCC‐135 exerts neuroprotective and antiepileptic effects by downregulating NCX1 expression, thereby alleviating calcium overload and reducing glutamate levels in the hippocampus. We are the first to propose the role and mechanism of MCC‐135 in epilepsy treatment, providing novel insights into its potential as a therapeutic agent for epilepsy.
Reproduced under the paper's license (CC BY), from the paper cited above.
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Data
Datasets cited
- geo:GSE160189, at NCBI GEO; found in “Data Availability Statement”
Other data links
- ncbi.nlm.nih.gov/
geo , NCBI; found in the text, “Data Collection”
Data Availability Statement
Data was downloaded from the public database online at the GEO database under accession numbers GSE160189 (https://
Reproduced under the paper's license (CC BY), from the paper cited above.
Versions
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Version 1, 30 September 2026: the first record
Recorded: type, language, journal, volume, issue, pages, dates, 11 authors, 5 keywords, 12 MeSH terms, 45 references.
Cite
This paper
Liu, C., He, M., Li, R., Zheng, S., Sun, L., Gong, C., Qi, H., Qin, X., Gan, X., Wang, F., & Wu, Y. (2026). MCC-135 Exerts Antiepileptic and Neuroprotective Effects by Downregulating NCX1 Expression to Decrease Intracellular Calcium Overload in the Hippocampus. CNS neuroscience & therapeutics, 32(3), e70808. https://
BibTeX
@article{liu2026mcc,
author = {Liu, Chaoning and He, Min and Li, Rida and Zheng, Shouhuan and Sun, Lanfeng and Gong, Chi and Qi, Hengchang and Qin, Xinran and Gan, Xiaohang and Wang, Fang and Wu, Yuan},
title = {{MCC-135 Exerts Antiepileptic and Neuroprotective Effects by Downregulating NCX1 Expression to Decrease Intracellular Calcium Overload in the Hippocampus}},
journal = {CNS neuroscience \& therapeutics},
year = {2026},
month = mar,
volume = {32},
number = {3},
pages = {e70808},
publisher = {Wiley},
issn = {1755-5930},
doi = {10.1002/
url = {https://
pmid = {41772763},
pmcid = {PMC12953174}
}
RIS
TY - JOUR
AU - Liu, Chaoning
AU - He, Min
AU - Li, Rida
AU - Zheng, Shouhuan
AU - Sun, Lanfeng
AU - Gong, Chi
AU - Qi, Hengchang
AU - Qin, Xinran
AU - Gan, Xiaohang
AU - Wang, Fang
AU - Wu, Yuan
TI - MCC-135 Exerts Antiepileptic and Neuroprotective Effects by Downregulating NCX1 Expression to Decrease Intracellular Calcium Overload in the Hippocampus
T2 - CNS neuroscience & therapeutics
J2 - CNS Neurosci Ther
PY - 2026
DA - 2026/
VL - 32
IS - 3
SP - e70808
SN - 1755-5930
PB - Wiley
DO - 10.1002/
UR - https://
LA - en
ER -
CSL-JSON
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"author": [
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