RESUMEN
The brain's endogenous opioid and endocannabinoid systems are neuromodulatory of synaptic transmission, and play key roles in pain, memory, reward, and addiction. Recent clinical and pre-clinical evidence suggests that opioid use may be reduced with cannabinoid intake. This suggests the presence of a functional interaction between these two systems. Emerging research indicates that cannabinoids and opioids can functionally interact at different levels. At the cellular level, opioid and cannabinoids can have direct receptor associations, alterations in endogenous opioid peptide or cannabinoid release, or post-receptor activation interactions via shared signal transduction pathways. At the systems level, the nature of cannabinoid and opioid interaction might differ in brain circuits underlying different behavioral phenomenon, including reward-seeking or antinociception. Given the rising use of opioid and cannabinoid drugs, a better understanding of how these endogenous signaling systems interact in the brain is of significant interest. This review focuses on the potential relationship of these neural systems in addiction-related processes.
Asunto(s)
Cannabinoides , Trastornos Relacionados con Opioides , Analgésicos Opioides/farmacología , Cannabinoides/farmacología , Humanos , Péptidos Opioides , Trastornos Relacionados con Opioides/tratamiento farmacológico , Trastornos Relacionados con Opioides/metabolismo , RecompensaRESUMEN
CRISPR-Cas systems constitute the adaptive immune system of bacteria and archaea, as a sequence-specific nucleic acid targeting defense mechanism. The sequence-specific recognition and cleavage of Cas effector complexes has been harnessed to developed CRISPR-based technologies and drive the genome editing revolution underway, due to their efficacy, efficiency, and ease of implementation in a broad range of organisms. CRISPR-based technologies offer a wide variety of opportunities in genome remodeling and transcriptional regulation, opening new avenues for therapeutic and biotechnological applications. To repurpose CRISPR-Cas systems for these applications, the various elements of the system need to be first identified and functionally characterized in their native host. Bioinformatic tools are first used to identify putative CRISPR arrays and their associated genes, followed by a comprehensive characterization of the CRISPR-Cas system, encompassing predictions for guide and target sequences. Subsequently, interference assays and transcriptomic analyses should be performed to probe the functionality of the CRISPR-Cas system. Once an endogenous CRISPR-Cas system is characterized as functional, they can be readily repurposed by delivering an engineered synthetic CRISPR array or a small RNA guide for targeted gene manipulation. Alternatively, developing a plasmid-based system for heterologous expression of the necessary CRISPR components can enable exploitation in other organisms. Altogether, there is a wide diversity of native CRISPR-Cas systems in many bacteria and most archaea that await functional characterization and repurposing for genome editing applications in prokaryotes.