A pH-sensitive closed-loop nanomachine to control hyperexcitability at the single neuron level.

ABSTRACT: Epilepsy affects 1% of the general population and 30% of patients are resistant to antiepileptic drugs. Although optogenetics is an efficient antiepileptic strategy, the difficulty of illuminating deep brain areas poses translational challenges. Thus, the search of alternative light sources is strongly needed. Here, we develop pH-sensitive inhibitory luminopsin (pHIL), a closed-loop chemo-optogenetic nanomachine composed of a luciferase-based light generator, a fluorescent sensor of intracellular pH (E²GFP), and an optogenetic actuator (halorhodopsin) for silencing neuronal activity. Stimulated by coelenterazine, pHIL experiences bioluminescence resonance energy transfer between luciferase and E²GFP which, under conditions of acidic pH, activates halorhodopsin. In pri

SUBMITTER: Merolla A 

PROVIDER: S-EPMC11224301 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature