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Ann Neurol.-Zhejiang University of Traditional Chinese Medicine New Discovery: Anti-epileptic Therapy, New Mechanism of Drug Resistance

 Last Update: 2021-07-27
 Source: Internet
 Author: User

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Given a considerable partEpilepsy patients do not respond well to antiepileptic drugs (AEDs), drug resistance has become an issue in a clinical epilepsy difficult to solve, especially in the medial temporal lobe epilepsy (TLE)
.

The elusive drug resistance mechanism obscures the effective treatment goals

Epilepsy decodes the causes of drug-resistant epilepsy from a comprehensive perspective, which will definitely help to understand the mechanism of drug-resistant epilepsy and identify potential targets

To caspase-1 role in drug resistance in laboratory TLE tube under the film, they deepen the study: conducted various behavioral, immune fluorescence, molecular and electrophysiological experiments
.

immunity

They found that in rats induced by drug-resistant amygdala, the expression of activated caspase-1 was up-regulated in the cerebellum, but not in CA1
.

In rats induced by drug-resistant amygdala, the expression of activated caspase-1 was up-regulated in the cerebellum, but not in CA1
.

In rats induced by drug-resistant amygdala, the expression of activated caspase-1 was up-regulated in the cerebellum, but not in CA1

The pro-drug effect of caspase-1 under the cell membrane is mediated by interleukin-1β, which is dependent on its downstream inflammasome
.

Further electrophysiological results show that inhibition of caspase-1 reduces the excitability of subventricular pyramidal neurons by affecting the excitation/inhibition balance of presynaptic input

Importantly, the small molecule caspase-1 inhibitor CZL80 can attenuate the onset of drug-resistant TLE models and reduce the nerve excitability in brain slices of patients with drug-resistant TLE
.

These results support the hypothesis that the Caspase-1-interleukin-1β inflammatory pathway under the cell membrane is a new alternative mechanism for drug-resistant TLE , and suggest that Caspase-1 is a potential target
.

Hypothesis of Caspase-1-Interleukin-1β inflammatory pathway as a new alternative mechanism for drug-resistant TLE

Original source

Xu C, Zhang S, Gong Y, Nao J, Shen Y, Tan B, Xu S, Cui S, Ruan Y, Wang S, Wang Y, Chen Z.

Subicular caspase-1 contributes to pharmacoresistance in temporal lobe epilepsy.
Ann Neurol .
2021 Jul 20.

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