Protein kinases in natural versus drug reward

Amaral, Inês M.; Scheffauer, Laura; Hofer, Alex; Rawas, Rana El

doi:10.1016/j.pbb.2022.173472

Cited by 8 publications

(7 citation statements)

References 140 publications

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“…As discussed here, CaMKII may represent a molecular point of convergence in the regulation of maladaptive behaviours associated with both natural [61] and drug [53] abuse.…”

Section: Semaglutide and Calmodulinsmentioning

confidence: 91%

“…Overall, these considerations emphasize the relevance of CaMKII activity in the regulation of molecular pathways within both the drug-and natural-related reward system [61].…”

Section: Calmodulin Involvement In Both Drug and Natural Rewardsmentioning

confidence: 98%

“…CaMKII has been suggested to play an essential role in the processing of natural reward as well [61]. CaMKII autophosphorylation-deficient mice showed impairments in the natural reward-related social interaction process [62].…”

Section: Calmodulin Involvement In Both Drug and Natural Rewardsmentioning

confidence: 99%

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Semaglutide as a Possible Calmodulin Binder: Ligand-Based Computational Analyses and Relevance to Its Associated Reward and Appetitive Behaviour Actions

Floresta,

Arillotta,

Catalani

et al. 2024

Sci. Pharm.

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Semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, has gained considerable attention as a therapeutic agent for type 2 diabetes mellitus and obesity. Despite its clinical success, the precise mechanisms underlying its pharmacological effects remain incompletely understood. In this study, we employed ligand-based drug design strategies to investigate potential off-target interactions of semaglutide. Through a comprehensive in silico screening of semaglutide’s structural properties against a diverse panel of proteins, we have identified calmodulin (CaM) as a putative novel target of semaglutide. Molecular docking simulations revealed a strong interaction between semaglutide and CaM, characterized by favourable binding energies and a stable binding pose. Further molecular dynamics simulations confirmed the stability of the semaglutide–CaM complex, emphasizing the potential for a physiologically relevant interaction. In conclusion, our ligand-based drug design approach has uncovered calmodulin as a potential novel target of semaglutide. This discovery sheds light on the complex pharmacological profile of semaglutide and offers a promising direction for further research into the development of innovative therapeutic strategies for metabolic disorders. The CaM, and especially so the CaMKII, system is central in the experience of both drug- and natural-related reward. It is here hypothesized that, due to semaglutide binding, the reward pathway-based calmodulin system may be activated, and/or differently regulated. This may result in the positive semaglutide action on appetitive behaviour. Further studies are required to confirm these findings.

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“…As discussed here, CaMKII may represent a molecular point of convergence in the regulation of maladaptive behaviours associated with both natural [61] and drug [53] abuse.…”

Section: Semaglutide and Calmodulinsmentioning

confidence: 91%

“…Overall, these considerations emphasize the relevance of CaMKII activity in the regulation of molecular pathways within both the drug-and natural-related reward system [61].…”

Section: Calmodulin Involvement In Both Drug and Natural Rewardsmentioning

confidence: 98%

See 1 more Smart Citation

Semaglutide as a Possible Calmodulin Binder: Ligand-Based Computational Analyses and Relevance to Its Associated Reward and Appetitive Behaviour Actions

Floresta,

Arillotta,

Catalani

et al. 2024

Sci. Pharm.

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“…The importance of the NAc shell in the processing of natural rewards, like SI, has been previously highlighted [ 65 ]. In one study, Amaral et al demonstrated that SI reward in rats induced an increase in the calcium/calmodulin-dependent protein kinase II (CaMKII) in the NAc of the brain.…”

Section: The Nucleus Accumbens Shell: a Pivotal Role In Si And Reward...mentioning

confidence: 99%

Orexins/Hypocretins: Gatekeepers of Social Interaction and Motivation

Ouaidat,

Amaral,

Monteiro

et al. 2024

IJMS

Self Cite

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Ever since the discovery of the brain’s orexin/hypocretin system, most research was directed toward unveiling its contribution to the normal functioning of individuals. The investigation of reward-seeking behaviors then gained a lot of attention once the distribution of orexinergic neurons was revealed. Here, we discuss findings on the involvement of orexins in social interaction, a natural reward type. While some studies have succeeded in defining the relationship between orexin and social interaction, the controversy regarding its nature (direct or inverse relation) raises questions about what aspects have been overlooked until now. Upon examining the literature, we identified a research gap concerning conditions influencing the impact of orexins on social behavior expression. In this review, we introduce a number of factors (e.g., stress, orexin’s source) that must be considered while studying the role of orexins in social interaction. Furthermore, we refer to published research to investigate the stage at which orexins affect social interaction and we highlight the nucleus accumbens (NAc) shell’s role in social interaction and other rewarding behaviors. Finally, the underlying orexin molecular pathway influencing social motivation in particular illnesses is proposed. We conclude that orexin’s impact on social interaction is multifactorial and depends on specific conditions available at a time.

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“…Long-term changes induced by psychostimulant exposure in these regions involve alterations in gene expression and cellular physiology [14,15]. Psychostimulant-induced synaptic plasticity is linked to the known mechanism of phosphorylation of extracellular signal-regulated kinases (ERK1/2) and cyclic adenosine 3 ′ ,5 ′ -monophosphate (cAMP)-response element-binding protein (CREB), with cAMP-dependent protein kinase (PKA) also playing a role in drug-induced memory formation [16][17][18][19]. However, the main challenge in addiction research remains the identification of cell types, gene/s, or different molecular markers capable of distinguishing natural from drug-induced alterations in the reward circuitry.…”

Section: Introductionmentioning

confidence: 99%

Breaking the Chains: Advances in Substance Addiction Research through Single-Cell Sequencing, Epigenetics, and Epitranscriptomic

Filošević Vujnović,

Stanković Matić,

Saftić Martinović

et al. 2024

Future Pharmacology

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Addiction is a complex brain disease influenced by genetic, environmental, and neurological factors. Psychostimulants, cocaine, and methamphetamine influence different cell types in different brain regions, with a focus on the neurons responsible for rewarding effects in the nucleus accumbens (NAc) and ventral tegmental area (VTA). Known markers for psychostimulant-induced neuronal plasticity in combination with droplet-based high-throughput single-cell sequencing divided the heterogeneity of cell populations in NAc and VTA into clusters, where all cells of the same type do not respond equally to exposure to psychostimulants. To explain psychostimulant-induced neuronal plasticity as changes in the amplitude and phase shifts of gene expression, we focused on epigenetic mechanisms of DNA and chromatin modifications, as well as DNA accessibility. We also comment on epitranscriptomics as a novel approach in the study of messenger RNA posttranslational modification, which regulates translation and potentially localized transcription in synapses in order to address the molecular chains that connect addiction from changes in gene expression to synaptic and, finally, neuronal plasticity.

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Protein kinases in natural versus drug reward

Cited by 8 publications

References 140 publications

Semaglutide as a Possible Calmodulin Binder: Ligand-Based Computational Analyses and Relevance to Its Associated Reward and Appetitive Behaviour Actions

Semaglutide as a Possible Calmodulin Binder: Ligand-Based Computational Analyses and Relevance to Its Associated Reward and Appetitive Behaviour Actions

Orexins/Hypocretins: Gatekeepers of Social Interaction and Motivation

Breaking the Chains: Advances in Substance Addiction Research through Single-Cell Sequencing, Epigenetics, and Epitranscriptomic

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