The viruses used in this article from BrainVTA are in the table below

The heat shock protein 70 (Hsp70) is upregulated in response to stress and has been implicated as a stress marker in temporal lobe epilepsy (TLE). However, whether Hsp70 plays a pathologic or protective role in TLE remains unclear. Here we report a deleterious role of Hsp70 in kainic acid (KA)-induced seizures. Hsp70 expression is upregulated in a KA model of TLE, and silencing or inhibition of Hsp70 suppresses neuronal hyperexcitability and attenuates acute or chronic epilepsy by enhancing A-type potassium current in hippocampal neurons. Hsp70 upregulation leads to proteosomal degradation of Kv4-KChIP4a channel complexes primarily encoding neuronal A-type current. Furthermore, Hsp70 directly binds to the N terminus of auxiliary KChIP4a and targets Kv4-KChIP4a complexes to proteasome. Taken together, our findings reveal a role of Hsp70 in the pathogenesis of epilepsy through degradation of Kv4-KChIP4a complexes, and pharmacological inhibition of Hsp70 may represent therapeutic potential for epilepsy or hyperexcitability-related neurological disorders.

Figure 1. Hsp70 Targets Kv4-KChIP4a Channel Complexes for Degradation

In the present study, the authors report an unexpected deleterious role of Hsp70 upregulation in a kainic acid (KA) model of temporal lobe epilepsy (TLE) in rats. The findings highlight an important role of Hsp70 in regulating neuronal excitability, and inhibition of Hsp70 may lead to a therapeutic strategy for epilepsy or other hyperexcitability-related neurological disorders.
 
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