Topic: Photopharmacology

Photopharmacology is an emerging approach that allows the spatiotemporal control of receptor function using photodrugs and offers superior tissue specificity and reduced off-target effects. Previously, we successfully demonstrated the blockade the adenosine A2A receptor (A2AR) in mouse brain using MRS7145, a photocaged derivative of the selective A2AR antagonist SCH442416.1 Here, we explore the use of bioluminescence resonance energy transfer (BRET) to photouncage MRS7145 in vitro and in vivo. First, we demonstrated the effective release of SCH442416 by BRET uncaging or bioluminolysis of MRS71

Inhibitory neurotransmission in the brain is mainly mediated by GABAARs. Disequilibrium in their function leads to many sever neurological disorders, such as epilepsy, anxiety, depression. Thus, development of allosteric modulators that would regulate the activity of these receptors with minimized side effects is of great importance. Photopharmacology is a unique tool for these purposes allowing precise spatial and temporal light-driven control of pharmacophores´ activity, and consequently of their target proteins.Pursuing the goal to develop a GABAARs positive photomodulator, we successfully

The adenosine A1 receptor (A1R) is a promising therapeutic target in epilepsy by mediating neuronal inhibition. In this study, we investigated whether A1R signaling is still functional in the intrahippocampal kainic acid (IHKA) mouse model for temporal lobe epilepsy (TLE). Moreover, we evaluated the feasibility of spatial selective inhibition of specific hippocampal subregions through photopharmacology. Electrically evoked field postsynaptic potentials (fPSPs) were recorded in the CA1 and DG of acute hippocampal slices. The effect of adding 40 nM of the A1R agonist N6cyclopentyladenosine (CPA)

The glutamatergic receptor mGlu5, being a modulator of neurotransmission in regions such as the cortex and hippocampus, plays a crucial role in learning and memory processing. Numerous studies highlight the alteration, contribution, and potential therapeutic targeting of mGlu5 in Alzheimer disease (AD). AD is the first cause of dementia, resulting in significant cognitive deficits, including memory loss due to the accumulation of Aβ, hyperphosphorylated tau, and neurodegeneration. In patients, brain asymmetric alterations, as Aβdepositions more pronounced in the left side, are reported early i