Hsp90β inhibitors prevent GLT-1 degradation but have no beneficial efficacy on absence epilepsy

Abstract

The loss of glutamate transporter-1 (GLT-1) is associated with temporal lobe epilepsy (TLE). A recent study reported that Hsp90β interacted with GLT-1 and recruited it to 20S proteasome for degradation. Therefore, inhibiting Hsp90β may be a new strategy for treating epilepsy. So far, no studies have shown whether the inhibition of Hsp90β had therapeutic effects on absence epilepsy. Using a model of absence epilepsy, we demonstrated that 17-allylamino-17-demethoxygeldanamycin (17AAG) and Ganetespib (STA9090) had no therapeutic effect. Although this is a negative result, it also has a meaningful exploration value for whether Hsp90 inhibitors have therapeutic effects on other epilepsy types.

Graphical Abstract

Keywords:

• Hsp90β inhibitor
• epilepsy
• GLT-1
• absence epilepsy

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This study was financially supported by CAMS Innovation Fund for Medical Sciences (no. 2017-I2M-2-004), and Beijing Key Laboratory of New Drug Mechanisms and Pharmacological Evaluation Study (BZ0150).