Publications by authors named "Rafael Rivas-Santisteban"
Article Synopsis
- GPR88 is an orphan G protein-coupled receptor primarily found in the striatum, and its function is not well understood despite changes in its expression seen in Parkinson's disease models.
- GPR88 was found to interact with the kappa-opioid receptor (KOR), and this interaction inhibits KOR-mediated signaling, as evidenced by experiments showing that GPR88 can modulate effects of KOR agonists in both cultured cells and primary striatal neurons.
- The GPR88-KOR complexes were more common in specific neurons related to dopamine pathways, suggesting that understanding their relationship could have implications for conditions like neuropathic pain, Parkinson's disease, and neuropsychiatric disorders.
Article Synopsis
- - Calcium ion (Ca) homeostasis is essential for proper neuron function, and this study investigated how the CB receptor (CBR) interacts with the ATR receptor to regulate cytoplasmic Ca levels in CNS neurons.
- - A specific type of interaction called AT-CB receptor heteromers (ATCBHets) was identified using bioluminescence resonance energy transfer (BRET) in lab cells and in the context of Parkinson's disease (PD).
- - The study found that activation of ATR reduces Ca levels in the presence of cannabinoids, and in a rat model of PD, lower levels of ATCBHets were linked to lesioned neurons, suggesting that cannabinoids might help mitigate calcium imbalance related to levodopa-induced
Article Synopsis
- Olfactory receptors are essential for our sense of smell and influence behaviors like food preferences and emotional memories.
- They have unique regenerative abilities that can provide insights into neural regeneration, which is crucial for addressing central nervous system injuries.
- Exploring the ectopic expression of these receptors may lead to new therapeutic approaches for repairing neural damage and treating neurodegenerative diseases.
Article Synopsis
- The text discusses the need for better tools to measure neuroprotection in Alzheimer's and Parkinson's diseases, emphasizing that current methods lack specific markers.
- It outlines the main outcome measures used in clinical trials for these neurodegenerative diseases since 2018, noting that they do not specifically assess neuroprotection.
- Finally, the text highlights the potential of metabolomics, utilizing body fluids to discover new biomarkers related to neuroprotection, thanks to recent advancements in technology that allow for better detection of relevant metabolites.
Article Synopsis
- Stroke is a major global health issue, affecting 15 million people annually and leaving millions dead or disabled, highlighting the need for new treatments to prevent cognitive decline and neuronal death.
- Phytocannabinoids are traditional compounds known for their neuroprotective benefits, but their psychoactive effects have limited their use in medicine, prompting research for non-psychoactive alternatives.
- Advances in cannabinoid receptor research, including the development of heteromers and the approval of certain CBD and Δ-THC combinations for specific conditions, represent promising new therapeutic avenues for neurodegenerative diseases and other disorders.
Article Synopsis
- Multiple sclerosis (MS) is a serious autoimmune and neurodegenerative disease affecting the central nervous system, with no cure available, highlighting the need for new treatment options.
- The endocannabinoid system (ECS) has a crucial role in brain functions, and recent studies have shown that cannabinoid receptor interactions (heteromers) are relevant in neurodegenerative diseases, but their specific role in MS remains unclear.
- New research identified cannabinoid receptor complexes (CBR-GPR55) in the prefrontal cortex, showing increased presence in MS patients, suggesting these receptor complexes could be potential targets for future MS therapies.
Article Synopsis
- The medial prefrontal cortex (mPFC) plays a crucial role in cognitive functions like working memory, and the astrocytic cannabinoid type 1 receptor (CB1R) affects calcium (Ca) signaling linked to neuronal activity.
- Research shows that adenosine A1 and A2A receptors (AR, A2AR) can modulate CB1R function in mPFC astrocytes, influencing how calcium signaling operates in these cells.
- The activation of CB1R enhances long-term potentiation (LTP) in the mPFC, which is regulated by A1 receptors, while in specific genetically modified mice lacking certain calcium responses, CB1R activation reduces LTP, suggesting a balanced
Article Synopsis
- * It utilizes a new method, MolBoolean, to analyze the interaction between these receptors in rats and monkeys, revealing that a high percentage of DR receptors interact with AR receptors, especially in a PD model.
- * The findings suggest that the functioning of DR in certain neurons is regulated by AR, indicating potential benefits of using adenosine receptor blockers as an early treatment for Parkinson's disease.
Article Synopsis
- The renin angiotensin system (RAS) is a network in the body that includes various signaling peptides, enzymes, and receptors, which has led to the development of antihypertensives, but its role in the brain is less understood.
- Recent findings suggest that RAS components in dopaminergic neurons may offer hope for treating Parkinson's disease by affecting the production of dopamine and regulating important enzymes like glucose-6-phosphate dehydrogenase, which is crucial for both dopamine synthesis and detoxifying reactive oxygen species.
- Activation of angiotensin II receptors can influence the activity of glucose-6-phosphate dehydrogenase, potentially enhancing neuronal health, but further research is necessary to explore how to pharmacologically enhance
Article Synopsis
- The N-methyl-D-aspartate receptor (NMDAR) interacts with the human prion protein (PrPC), which negatively influences NMDAR signaling and may be linked to Alzheimer's disease pathology.
- Advanced methods revealed that this interaction can lead to increased neurotoxicity and neuronal death, particularly in neurons from an Alzheimer's mouse model.
- The study suggests that overexpression of NMDAR-PrPC complexes in these neurons could contribute to the progression of Alzheimer's disease.
Article Synopsis
- The potential of cannabinoid (CB) and angiotensin (AT) receptors as therapeutic targets for Parkinson's disease (PD) is highlighted, particularly their interaction in brain circuits.
- Research has shown that CB receptors can directly interact with AT receptors, leading to increased G-signaling, and this interaction is present in both lab systems and in primary neurons.
- In a rodent model of PD, increased levels of CB-AT receptor complexes were observed in the striatum of rats that developed dyskinesia after levodopa treatment, suggesting that targeting CB receptors may have implications for both addictive behaviors and neurodegenerative diseases.
Article Synopsis
- The study suggests that orexin may influence amyloid beta peptide levels in a model of Alzheimer's disease, indicating a link between orexin and CBR in microglial regulation.
- The research highlights the formation of CB-OX receptor complexes in microglia, which may enhance neuroprotection when activated.
- Findings indicate that using OXR antagonists can amplify the effects of CBR activation, presenting a potential therapeutic strategy for Alzheimer's disease treatment.
Article Synopsis
- Extracellular adenosine builds up in many tumors, prompting research into using adenosine receptors (ARs) as potential cancer treatment targets.
- The four identified ARs, A, A, A, and A, are part of the G protein-coupled receptors family and play roles in tumor progression and immune response regulation.
- This review specifically examines the effectiveness of A and A receptor antagonists in cancer therapy, highlighting their potential to enhance chemotherapy and immunotherapy, along with ongoing clinical trials testing these AR ligands.
Article Synopsis
- The study compared the effects of Δ-THCA and Δ-THCV with Δ-THC by examining their binding to human cannabinoid receptors CB1, CB2, and heteromers in living cells.
- Differential signaling outcomes were found, indicating that the effects of these cannabinoids vary based on the specific receptor and the structure of the compound used, showing variability in how they activate different pathways.
- Results suggest that cannabinoids can bind in various ways, leading to different physiological effects depending on the receptor type and which signaling pathways are activated.
Article Synopsis
- The study explores the interaction between cannabinoid CB receptors and NMDA receptors, suggesting cannabinoids may modulate NMDA functions, which could be beneficial for Alzheimer's disease treatment.
- Methods included advanced techniques like immunocytochemistry and bioluminescence resonance energy transfer to analyze receptor complexes in neurons and glial cells, particularly in Alzheimer's disease model mice.
- Results revealed that cannabinoid activation dampens NMDA receptor signaling, with increased expression of CB-NMDA complexes in Alzheimer's model mice, indicating potential therapeutic avenues for managing excitatory neurotransmission in dementia.
Article Synopsis
- Cannabinoids can stimulate appetite, influenced by the hunger hormone ghrelin, and this research investigates how they interact at the level of brain receptors.
- The study identified complexes between cannabinoid receptors and ghrelin receptors in brain cells, suggesting these interactions can alter receptor signaling.
- High-fat diet exposure in pregnant mice resulted in increased formation of these receptor complexes in their offspring's brain neurons, indicating a potential link to obesity risk.
Article Synopsis
- ACE2 is essential for regulating oxidative stress and inflammation in the body and serves as the entry point for the SARS-CoV-2 virus.
- Research shows that ACE2 and its products are concentrated in mitochondria and interact with a receptor called MrgE, leading to the production of nitric oxide, which is crucial for cellular function.
- Changes in the levels of ACE2, MrgE, and associated oxidative stress markers in the brain may contribute to neurodegenerative diseases and could also influence how SARS-CoV-2 affects cells.
Article Synopsis
- Neuronal health relies heavily on glial support, primarily from astroglial and microglial cells, which are crucial for neuronal survival during both neurodegenerative diseases and aging.
- Activated microglia display two key forms: the pro-inflammatory M1 type, which can be harmful, and the neuroprotective M2 type, which helps combat chronic inflammation.
- Achieving a balance between M1 and M2 microglia is vital for neuronal survival, and targeting G protein-coupled receptors, especially adenosine receptors, could enhance the neuroprotective M2 response and improve microglial function during stress events.
Article Synopsis
- 5-hydroxytryptamine (5-HT) is a neurotransmitter derived from the amino acid L-tryptophan and has receptors in various mammalian cells, affecting both the nervous system and other bodily systems.
- In contrast, glutamate (Glu) and ATP are mainly known for their roles in metabolism, yet they also function as neurotransmitters with receptors present in multiple cell types.
- All three molecules (5-HT, ATP, and Glu) act through G protein-coupled receptors and ionotropic receptors, highlighting their importance as holistic regulators within the body.
Article Synopsis
- The study reviews the role of gene mutations in familial Parkinson's disease (PD) and their potential impact on dopaminergic neuron degeneration, focusing on α-synuclein (α-syn) aggregation.
- Utilizing the STRING database, the authors explore interactions between genes and propose mechanisms involving altered α-syn processing or vesicular trafficking linked to mitochondrial energy requirements.
- The research suggests that targeting G protein-coupled receptors in neuronal mitochondria could help alleviate oxidative stress and improve mitochondrial function in PD.
Article Synopsis
- Biased signaling in G protein-coupled receptors (GPCRs) leads to varied signaling outputs based on the specific chemical structure of agonists.
- The review explores established mechanisms for biased agonism, like the induced fit hypothesis and key/lock hypothesis, while examining how different agonists can produce distinct outcomes.
- The context of receptor interactions, particularly receptor-receptor heteromerization, is crucial for understanding functional selectivity and optimizing the design of biased agonists for drug development.
Article Synopsis
- The renin-angiotensin system (RAS) regulates blood pressure and maintains homeostasis in mammals, with recent interest due to its connection to SARS viruses through ACE2.
- The study aimed to explore interactions between Mas and angiotensin receptors, using techniques like resonance energy transfer to investigate their functionality in neurons and microglia.
- Findings revealed that Mas and angiotensin receptors can form heterotrimers and that their signaling is affected by microglial activation, suggesting a complex regulatory mechanism that may have implications for neurodegenerative disease therapies.
Article Synopsis
- ACE2 is a key enzyme in the renin-angiotensin system and serves as a receptor for SARS coronaviruses, though its exact mechanism of entry into cells is unclear.
- Studies suggest that ACE2 can interact with specific receptors related to the RAS, such as angiotensin II type 1 and type 2 receptors, and these interactions may influence cell signaling and the expression of ACE2 on cell surfaces.
- The research indicates that ACE2 complexes in lung tissue could play a significant role in SARS-CoV-2 infection and may offer new opportunities for therapeutic interventions.
Article Synopsis
- Three major neurodegenerative diseases—Parkinson's, Alzheimer's, and Huntington's—are being researched for potential treatment using cannabinoids to protect brain cells and slow disease progression.
- Recent studies, particularly since 2016, suggest that cannabinoids can interact with various receptors in the brain to provide neuroprotection, and there's a promising focus on targeting glial cannabinoid receptors to reduce side effects.
- The approval of cannabis extracts like SativexTM for human therapy paves the way for broader legal use of cannabinoids, enhancing their potential as viable treatments for neurodegenerative disorders.
Article Synopsis
- Biased agonism allows different signaling outcomes by stabilizing specific receptor shapes in GPCR signaling, emphasizing the role of the C-terminal domain in functional selectivity.
- The study compares the full-length adenosine A receptor (AR) and a truncated version lacking the last 40 amino acids to see how various agonists affect intracellular pathways important for diseases like Parkinson's.
- Experimental data indicate that while the C-terminus isn’t crucial for G-protein or β-arrestin recruitment, significant differences in signaling bias arise from certain agonists like PSB-0777 and LUF-5834, highlighting the importance of receptor structure.