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.

• Authors: Yu-Chen Peng, Shan Wang, Yong Zhang, Long-Jian Huang, Xiao-Liang Wang, Ying Peng
• Journal: Journal of Asian natural products research (J Asian Nat Prod Res) Vol. 21 Issue 9 Pg. 905-915 (Sep 2019) ISSN: 1477-2213 [Electronic] England
• PMID: 30450970 (Publication Type: Journal Article)

Chemical References

• Anticonvulsants
• Benzoquinones
• Excitatory Amino Acid Transporter 2
• Glial Fibrillary Acidic Protein
• HSP90 Heat-Shock Proteins
• Hsp90b1 protein, mouse
• Lactams, Macrocyclic
• STA 9090
• Slc1a2 protein, mouse
• Triazoles
• glial fibrillary astrocytic protein, mouse
• tanespimycin
• Pentylenetetrazole

Topics

• Animals
• Anticonvulsants (chemistry, pharmacology)
• Benzoquinones (chemistry, pharmacology)
• Epilepsy, Absence (chemically induced, drug therapy)
• Excitatory Amino Acid Transporter 2 (metabolism)
• Gene Expression Regulation (drug effects)
• Glial Fibrillary Acidic Protein (genetics, metabolism)
• HSP90 Heat-Shock Proteins (antagonists & inhibitors)
• Hippocampus (metabolism)
• Lactams, Macrocyclic (chemistry, pharmacology)
• Mice
• Pentylenetetrazole (toxicity)
• Triazoles (chemistry, pharmacology)