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The targeting of the endogenous cannabinoid system has emerged as a promising therapeutic strategy against several neurodegenerative diseases. In this chapter, we discuss the rationale behind the potential utility of modulating cannabinoid receptor signaling to alleviate symptoms and curtail the progression of neurodegenerative diseases. Moreover, we describe an innovative methodology to evaluate the pharmacological activity of potential novel cannabinoid ligands and the functional interaction between cannabinoid receptors and other G protein-coupled receptors. Specifically, we detail the protocols for using NanoLuc Binary Technology (NanoBiT®) and Proximity Ligation In Situ Assay (P-LISA) to assess cannabinoid receptor signaling and receptor heteromerization dynamics both in living cells and ex vivo by using cannabinoid CB1 and adenosine A2A receptors as examples. A comprehensive understanding of the pharmacology of cannabinoid receptors is essential to accelerate drug development against neurodegenerative diseases based on the modulation of the endogenous cannabinoid system.

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Targeting Cannabinoid Receptors Against Neurodegenerative Diseases: NanoLuc Binary Technology and Proximity Ligation In Situ Assay to Evaluate Pharmacological Activity of Novel Compounds and Receptor Heteromerization

  • 实验方案

  • 发表日期：

    2025年

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  • Nuria Sánchez-Fernández,
  • Laura Gómez-Acero,
  • Francisco Ciruela,
  • Ester Aso

摘要

The targeting of the endogenous cannabinoid system has emerged as a promising therapeutic strategy against several neurodegenerative diseases. In this chapter, we discuss the rationale behind the potential utility of modulating cannabinoid receptor signaling to alleviate symptoms and curtail the progression of neurodegenerative diseases. Moreover, we describe an innovative methodology to evaluate the pharmacological activity of potential novel cannabinoid ligands and the functional interaction between cannabinoid receptors and other G protein-coupled receptors. Specifically, we detail the protocols for using NanoLuc Binary Technology (NanoBiT®) and Proximity Ligation In Situ Assay (P-LISA) to assess cannabinoid receptor signaling and receptor heteromerization dynamics both in living cells and ex vivo by using cannabinoid CB1 and adenosine A2A receptors as examples. A comprehensive understanding of the pharmacology of cannabinoid receptors is essential to accelerate drug development against neurodegenerative diseases based on the modulation of the endogenous cannabinoid system.