| 研究実績の概要 |
We previously developed the first positive allosteric modulator of adenosine A2A receptors (A2AR), named A2AR PAM-1, that evokes A2AR responses in the brain (e.g., sleep induction) without affecting cardiovascular function, unlike classic A2AR agonists. We are now collaborating with the Abe Lab (Hiroshima University, Graduate School of Advanced Science and Engineering) to develop a visible-light (420 nm) photoactivatable (‘caged’) A2AR PAM-1. Using the opto-version of the A2AR PAM, we, for the first time, optochemically induced sleep in freely behaving mice and demonstrated that extracellular adenosine produced by glia and neurons in nucleus accumbens promotes sleep [Roy K et al., in preparation].
|
| 現在までの達成度 (区分) |
現在までの達成度 (区分)
2: おおむね順調に進展している
理由
In addition to developing a new tool for optochemical control of extracellular adenosine, we have installed equipment for single-cell gene expression profiling, including a 10X Genomics Controller for feature barcoding, an S2 Singulator 100 for single nuclei preparation, and a workstation for data analysis. We are now able to rapidly generate insights that are critical for understanding glia-neuron interactions during sleep at the molecular level.
|
| 今後の研究の推進方策 |
In the future, pharmacotherapy may offer the possibility to cure diseases and alleviate symptoms while preventing uncontrolled drug activity in time and space, i.e. the drug is only active at times and sites where it produces its therapeutic effect. Our approach should aid in the generation of visible-light photocactivatable compounds for virtually any druggable target.
|
