Pub Date : 2024-08-09DOI: 10.3390/receptors3030019
Daniel D Bikle
Chronic skin wounds are estimated to affect 6.5 million patients in the US, at a cost of over USD 25 billion. Efforts to prevent and/or treat such wounds will result in reduced morbidity and economic losses. This project is focused on the role of vitamin D signaling in the epidermis in the control of stem cell (SC) activation and function during the initial response to the wounding of the skin, a response that, if defective, contributes to poor wound healing or cancer. In this review, I first describe the anatomy of the skin, focusing first on the epidermis, describing the different cell layers which in a spatial way also represent the differentiation process of the interfollicular epidermis (IFE) as it undergoes continuous regeneration. I then describe the other components of the skin, particularly the hair follicle (HF), which undergoes a cyclic pattern of regeneration. Adult SCs residing in these regenerative tissues play essential roles in the maintenance of these tissues. However, when the skin is wounded, the progeny of SCs from all regions of the HF and IFE contribute to the healing process by changing their initial cell fate to take on an epithelial genotype/phenotype to heal the wound. Although earlier lineage tracing studies helped to define the contributions SCs from the different niches made to wound healing, scRNAseq studies have demonstrated a considerably more nuanced picture. The role of vitamin D signaling will be introduced by reviewing the unique role played by the epidermal keratinocyte first in producing vitamin D and then in metabolizing it into its active form 1,25(OH)2D. 1,25(OH)2D is the principal ligand for the vitamin D receptor (VDR), a transcription factor that helps to mediate the genomic changes in the stem cells in their response to wounding. In these actions, the VDR is regulated by coregulators, of which the steroid receptor coactivator complexes SRC 2 and 3 and the mediator complex (MED) play essential roles. The VDR generally acts in association with other transcription factors such as p63 and β-catenin that can colocalize with the VDR in the genes it regulates. Although much remains to be understood, the role of the VDR in the stem cell response to wounding is clearly essential and quite different from its classic roles in regulating calcium metabolism, although calcium is essential for the actions of vitamin D signaling in the skin.
{"title":"The Role of the Vitamin D Receptor in the Epidermal Stem Cell Response to Wounding","authors":"Daniel D Bikle","doi":"10.3390/receptors3030019","DOIUrl":"https://doi.org/10.3390/receptors3030019","url":null,"abstract":"Chronic skin wounds are estimated to affect 6.5 million patients in the US, at a cost of over USD 25 billion. Efforts to prevent and/or treat such wounds will result in reduced morbidity and economic losses. This project is focused on the role of vitamin D signaling in the epidermis in the control of stem cell (SC) activation and function during the initial response to the wounding of the skin, a response that, if defective, contributes to poor wound healing or cancer. In this review, I first describe the anatomy of the skin, focusing first on the epidermis, describing the different cell layers which in a spatial way also represent the differentiation process of the interfollicular epidermis (IFE) as it undergoes continuous regeneration. I then describe the other components of the skin, particularly the hair follicle (HF), which undergoes a cyclic pattern of regeneration. Adult SCs residing in these regenerative tissues play essential roles in the maintenance of these tissues. However, when the skin is wounded, the progeny of SCs from all regions of the HF and IFE contribute to the healing process by changing their initial cell fate to take on an epithelial genotype/phenotype to heal the wound. Although earlier lineage tracing studies helped to define the contributions SCs from the different niches made to wound healing, scRNAseq studies have demonstrated a considerably more nuanced picture. The role of vitamin D signaling will be introduced by reviewing the unique role played by the epidermal keratinocyte first in producing vitamin D and then in metabolizing it into its active form 1,25(OH)2D. 1,25(OH)2D is the principal ligand for the vitamin D receptor (VDR), a transcription factor that helps to mediate the genomic changes in the stem cells in their response to wounding. In these actions, the VDR is regulated by coregulators, of which the steroid receptor coactivator complexes SRC 2 and 3 and the mediator complex (MED) play essential roles. The VDR generally acts in association with other transcription factors such as p63 and β-catenin that can colocalize with the VDR in the genes it regulates. Although much remains to be understood, the role of the VDR in the stem cell response to wounding is clearly essential and quite different from its classic roles in regulating calcium metabolism, although calcium is essential for the actions of vitamin D signaling in the skin.","PeriodicalId":507548,"journal":{"name":"Receptors","volume":"92 8","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141921781","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-11DOI: 10.3390/receptors3030017
C. A. Elizalde-Romero, N. Leyva-López, L. Contreras-Angulo, Rigoberto Cabanillas Ponce de-León, L. Z. Rodriguez-Anaya, J. León‐Félix, J. B. Heredia, S. Beltrán-Ontiveros, E. P. Gutiérrez-Grijalva
Overweight and obesity are global health and economic concerns. This disease can affect every system of the human body and can lead to complications such as metabolic syndrome, diabetes, cancer, dyslipidemia, cardiovascular diseases, and hypertension, among others. Treatment may sometimes include diet, exercise, drugs, and bariatric surgery. Nonetheless, not all people have access to these treatments, and public health strategies consider prevention the most important factor. In this regard, recent investigations are aiming to find alternatives and adjuvants for the treatment of obesity, its prevention, and the reversion of some of its complications, using natural sources of anti-obesogenic compounds like polyphenols, terpenes, alkaloids, and saponins, among others. In this review, we gather the most current information using PubMed, Google Scholar, Scopus, Cochrane, and the Web of Science. We present and discuss the current information about natural products that have shown anti-obesogenic effects at a molecular level. We also consider the impact of dietary habits and lifestyle on preventing overweight and obesity due to the evidence of the benefits of certain foods and compounds consumed regularly. We discuss mechanisms, pathways, and receptors involved in the modulation of obesity, especially those related to inflammation and oxidative stress linked to this disease, due to the relevance of these two aspects in developing complications.
超重和肥胖是全球关注的健康和经济问题。这种疾病会影响人体的各个系统，并可能导致代谢综合征、糖尿病、癌症、血脂异常、心血管疾病和高血压等并发症。治疗方法有时包括饮食、运动、药物和减肥手术。然而，并非所有人都能获得这些治疗，公共卫生战略认为预防是最重要的因素。在这方面，最近的研究旨在利用多酚、萜烯、生物碱和皂苷等天然抗肥胖化合物，寻找治疗肥胖症、预防肥胖症和逆转肥胖症并发症的替代品和辅助剂。在这篇综述中，我们利用 PubMed、Google Scholar、Scopus、Cochrane 和 Web of Science 收集了最新信息。我们介绍并讨论了在分子水平上显示出抗致肿作用的天然产品的最新信息。我们还考虑了饮食习惯和生活方式对预防超重和肥胖的影响，因为有证据表明经常食用某些食物和化合物对预防超重和肥胖有益。我们还讨论了调节肥胖的机制、途径和受体，特别是与炎症和氧化应激有关的机制、途径和受体，因为这两方面与肥胖症并发症的发生息息相关。
{"title":"Current Evidence of Natural Products against Overweight and Obesity: Molecular Targets and Mechanisms of Action","authors":"C. A. Elizalde-Romero, N. Leyva-López, L. Contreras-Angulo, Rigoberto Cabanillas Ponce de-León, L. Z. Rodriguez-Anaya, J. León‐Félix, J. B. Heredia, S. Beltrán-Ontiveros, E. P. Gutiérrez-Grijalva","doi":"10.3390/receptors3030017","DOIUrl":"https://doi.org/10.3390/receptors3030017","url":null,"abstract":"Overweight and obesity are global health and economic concerns. This disease can affect every system of the human body and can lead to complications such as metabolic syndrome, diabetes, cancer, dyslipidemia, cardiovascular diseases, and hypertension, among others. Treatment may sometimes include diet, exercise, drugs, and bariatric surgery. Nonetheless, not all people have access to these treatments, and public health strategies consider prevention the most important factor. In this regard, recent investigations are aiming to find alternatives and adjuvants for the treatment of obesity, its prevention, and the reversion of some of its complications, using natural sources of anti-obesogenic compounds like polyphenols, terpenes, alkaloids, and saponins, among others. In this review, we gather the most current information using PubMed, Google Scholar, Scopus, Cochrane, and the Web of Science. We present and discuss the current information about natural products that have shown anti-obesogenic effects at a molecular level. We also consider the impact of dietary habits and lifestyle on preventing overweight and obesity due to the evidence of the benefits of certain foods and compounds consumed regularly. We discuss mechanisms, pathways, and receptors involved in the modulation of obesity, especially those related to inflammation and oxidative stress linked to this disease, due to the relevance of these two aspects in developing complications.","PeriodicalId":507548,"journal":{"name":"Receptors","volume":"41 10","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141658535","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-03DOI: 10.3390/receptors3030016
Arvee Prajapati, Shagun Rangra, Rashmi Patil, Nimeet Desai, V. G. Jyothi, Sagar Salave, Prakash Amate, Derajram Benival, Nagavendra Kommineni
Receptor-targeted drug delivery has been extensively explored for active targeting of therapeutic moiety in cancer treatment. In this review, we discuss the receptors that are overexpressed on tumor cells and have the potential to be targeted by nanocarrier systems for cancer treatment. We also highlight the different types of nanocarrier systems and targeting ligands that researchers have explored. Our discussion covers various therapeutic modalities, including small molecules, aptamers, peptides, antibodies, and cell-based targeting strategies, and focuses on clinical developments. Additionally, this article highlights the challenges that arise during the clinical translation of nanocarrier-based targeting strategies. It also provides future directions for improving research in the area of clinically translatable cancer-targeted therapy to improve treatment efficacy while minimizing toxicity.
{"title":"Receptor-Targeted Nanomedicine for Cancer Therapy","authors":"Arvee Prajapati, Shagun Rangra, Rashmi Patil, Nimeet Desai, V. G. Jyothi, Sagar Salave, Prakash Amate, Derajram Benival, Nagavendra Kommineni","doi":"10.3390/receptors3030016","DOIUrl":"https://doi.org/10.3390/receptors3030016","url":null,"abstract":"Receptor-targeted drug delivery has been extensively explored for active targeting of therapeutic moiety in cancer treatment. In this review, we discuss the receptors that are overexpressed on tumor cells and have the potential to be targeted by nanocarrier systems for cancer treatment. We also highlight the different types of nanocarrier systems and targeting ligands that researchers have explored. Our discussion covers various therapeutic modalities, including small molecules, aptamers, peptides, antibodies, and cell-based targeting strategies, and focuses on clinical developments. Additionally, this article highlights the challenges that arise during the clinical translation of nanocarrier-based targeting strategies. It also provides future directions for improving research in the area of clinically translatable cancer-targeted therapy to improve treatment efficacy while minimizing toxicity.","PeriodicalId":507548,"journal":{"name":"Receptors","volume":"12 10","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141681340","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Insect-transmitted plant viruses are a major threat to global agricultural crop production. Receptors play a prominent role in the interplay between host-pathogen and vector interaction. The virus–vector relationship involves both viral and vector receptors. Receptors-like kinases (RLKs) and receptor-like proteins play a crucial role in plant immunity, which acts as a basal defense. Pathogens can evade or block host recognition by their effector proteins to inhibit pathogen recognition receptor (PRR)-mediated signaling. Intriguingly, RLKs are also known to interact with viral proteins and impact plant susceptibility against viruses, while the endocytic receptors in vectors assist in the binding of the virus to the vectors. Unlike other receptors of fungi and bacteria which have three different domains located from extracellular or intracellular to perceive a multitude of molecular patterns, the characterization of viral receptors is quite complex and limited since the virus is directly injected into plant cells by insect vectors. Little is known about these receptors. Unraveling the receptors involved in virus entry and transmission within the vector will provide vital information in virus–vector interactions. This review focuses on efforts undertaken in the identification and characterization of receptors of plant viruses within the host and vector. This will lead to a better understanding of the cellular mechanism of virus transmission and spread, and further suggests new alternative tools for researchers to develop an integrated approach for the management of viral diseases and associated vectors.
{"title":"Deciphering the Role of Virus Receptors in Plant–Virus–Vector Interactions","authors":"Sumit Jangra, Senthilraja Chinnaiah, Sneha Rashtrapal Patil, Bhavya Shukla, Ragunathan Devendran, Manish Kumar","doi":"10.3390/receptors3020013","DOIUrl":"https://doi.org/10.3390/receptors3020013","url":null,"abstract":"Insect-transmitted plant viruses are a major threat to global agricultural crop production. Receptors play a prominent role in the interplay between host-pathogen and vector interaction. The virus–vector relationship involves both viral and vector receptors. Receptors-like kinases (RLKs) and receptor-like proteins play a crucial role in plant immunity, which acts as a basal defense. Pathogens can evade or block host recognition by their effector proteins to inhibit pathogen recognition receptor (PRR)-mediated signaling. Intriguingly, RLKs are also known to interact with viral proteins and impact plant susceptibility against viruses, while the endocytic receptors in vectors assist in the binding of the virus to the vectors. Unlike other receptors of fungi and bacteria which have three different domains located from extracellular or intracellular to perceive a multitude of molecular patterns, the characterization of viral receptors is quite complex and limited since the virus is directly injected into plant cells by insect vectors. Little is known about these receptors. Unraveling the receptors involved in virus entry and transmission within the vector will provide vital information in virus–vector interactions. This review focuses on efforts undertaken in the identification and characterization of receptors of plant viruses within the host and vector. This will lead to a better understanding of the cellular mechanism of virus transmission and spread, and further suggests new alternative tools for researchers to develop an integrated approach for the management of viral diseases and associated vectors.","PeriodicalId":507548,"journal":{"name":"Receptors","volume":"45 36","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141269983","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-10DOI: 10.3390/receptors3020011
L. S. Frota, W. M. B. da Silva, Daniela Ribeiro Alves, Sacha Aubrey Alves Santos Rodrigues, Gabriela Alves do Nascimento, F. E. A. Magalhães, A. R. Campos, S. D. de Morais
The constant use of alcoholic beverages can deregulate serotonin levels, affecting neurotransmitters and triggering symptoms of anxiety. In this context, the objective of this work was to evaluate the anxiolytic potential and possible action mechanisms of the natural compound amentoflavone against the deleterious effects caused by alcohol withdrawal on the behavior of adult zebrafish (aZF). The experiments showed that amentoflavone did not change locomotion and did not cause toxicity in aZF during up to 96 h of analysis, with a median lethal concentration (LC50) greater than 1.0 mg/mL. The reversal of anxiety by pretreatment with granisetron suggested that the anxiolytic effect of amentoflavone is dependent on serotonergic 5-HT3A/3B receptors. Furthermore, amentoflavone reversed anxiety due to flumazenil pretreatment, suggesting a dependence on the GABAA receptor. The three concentrations of amentoflavone tested were effective in treating anxiety resulting from alcohol withdrawal. In silico analysis validated the in vivo results, supporting the idea that the interaction of amentoflavone with the protein occurs in a more stable manner than reference compounds. Amid growing interest in natural alternatives to treat anxiety disorders, amentoflavone is a potential candidate for a new anxiolytic compound that acts specifically on the 5HT3A/3B and GABAergic serotonergic pathways.
{"title":"An Evaluation of the Anxiolytic Potential of Amentoflavone in Adult Zebrafish Undergoing Alcohol Withdrawal: In Vivo and In Silico Studies","authors":"L. S. Frota, W. M. B. da Silva, Daniela Ribeiro Alves, Sacha Aubrey Alves Santos Rodrigues, Gabriela Alves do Nascimento, F. E. A. Magalhães, A. R. Campos, S. D. de Morais","doi":"10.3390/receptors3020011","DOIUrl":"https://doi.org/10.3390/receptors3020011","url":null,"abstract":"The constant use of alcoholic beverages can deregulate serotonin levels, affecting neurotransmitters and triggering symptoms of anxiety. In this context, the objective of this work was to evaluate the anxiolytic potential and possible action mechanisms of the natural compound amentoflavone against the deleterious effects caused by alcohol withdrawal on the behavior of adult zebrafish (aZF). The experiments showed that amentoflavone did not change locomotion and did not cause toxicity in aZF during up to 96 h of analysis, with a median lethal concentration (LC50) greater than 1.0 mg/mL. The reversal of anxiety by pretreatment with granisetron suggested that the anxiolytic effect of amentoflavone is dependent on serotonergic 5-HT3A/3B receptors. Furthermore, amentoflavone reversed anxiety due to flumazenil pretreatment, suggesting a dependence on the GABAA receptor. The three concentrations of amentoflavone tested were effective in treating anxiety resulting from alcohol withdrawal. In silico analysis validated the in vivo results, supporting the idea that the interaction of amentoflavone with the protein occurs in a more stable manner than reference compounds. Amid growing interest in natural alternatives to treat anxiety disorders, amentoflavone is a potential candidate for a new anxiolytic compound that acts specifically on the 5HT3A/3B and GABAergic serotonergic pathways.","PeriodicalId":507548,"journal":{"name":"Receptors","volume":" 13","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140992994","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-03DOI: 10.3390/receptors3020010
Harika Nagandla, Christoforos Thomas
Estrogen receptor (ER) β (ERβ) is the second ER subtype that mediates the effects of estrogen in target tissues along with ERα that represents a validated biomarker and target for endocrine therapy in breast cancer. ERα was the only known ER subtype until 1996 when the discovery of ERβ opened a new chapter in endocrinology and prompted a thorough reevaluation of the estrogen signaling paradigm. Unlike the oncogenic ERα, ERβ has been proposed to function as a tumor suppressor in breast cancer, and extensive research is underway to uncover the full spectrum of ERβ activities and elucidate its mechanism of action. Recent studies have relied on new transgenic models to capture effects in normal and malignant breast that were not previously detected. They have also benefited from the development of highly specific synthetic ligands that are used to demonstrate distinct mechanisms of gene regulation in cancer. As a result, significant new information about the biology and clinical importance of ERβ is now available, which is the focus of discussion in the present article.
{"title":"Estrogen Signals through ERβ in Breast Cancer; What We Have Learned since the Discovery of the Receptor","authors":"Harika Nagandla, Christoforos Thomas","doi":"10.3390/receptors3020010","DOIUrl":"https://doi.org/10.3390/receptors3020010","url":null,"abstract":"Estrogen receptor (ER) β (ERβ) is the second ER subtype that mediates the effects of estrogen in target tissues along with ERα that represents a validated biomarker and target for endocrine therapy in breast cancer. ERα was the only known ER subtype until 1996 when the discovery of ERβ opened a new chapter in endocrinology and prompted a thorough reevaluation of the estrogen signaling paradigm. Unlike the oncogenic ERα, ERβ has been proposed to function as a tumor suppressor in breast cancer, and extensive research is underway to uncover the full spectrum of ERβ activities and elucidate its mechanism of action. Recent studies have relied on new transgenic models to capture effects in normal and malignant breast that were not previously detected. They have also benefited from the development of highly specific synthetic ligands that are used to demonstrate distinct mechanisms of gene regulation in cancer. As a result, significant new information about the biology and clinical importance of ERβ is now available, which is the focus of discussion in the present article.","PeriodicalId":507548,"journal":{"name":"Receptors","volume":"13 49","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141016777","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-12DOI: 10.3390/receptors3020009
I. Kawahata, David I. Finkelstein, Kohji Fukunaga
Understanding the intricate role of dopamine D1–D5 receptors is pivotal in addressing the challenges posed by the aging global population, as well as by social stress and advancing therapeutic interventions. Central to diverse brain functions such as movement, cognition, motivation, and reward, dopamine receptors are ubiquitously distributed across various brain nuclei. This comprehensive review explores the nuanced functions of each dopamine receptor, D1, D2, D3, D4, and D5, in distinct brain regions, elucidating the alterations witnessed in several neurological and psychiatric disorders. From the substantia nigra and ventral tegmental area, crucial for motor control and reward processing, to the limbic system influencing emotional responses, motivation, and cognitive functions, each brain nucleus reveals a specific involvement of dopamine receptors. In addition, genetic variations in dopamine receptors affect the risk of developing schizophrenia and parkinsonism. The review further investigates the physiological significance and pathogenic impacts of dopamine receptors in critical areas like the prefrontal cortex, hypothalamus, and striatum. By unraveling the complexities of dopamine receptor biology, especially those focused on different brain nuclei, this review provides a foundation for understanding their varied roles in health and disease, which is essential for the development of targeted therapeutic strategies aimed at mitigating the impact of aging and mental health on neurological well-being.
{"title":"Dopamine D1–D5 Receptors in Brain Nuclei: Implications for Health and Disease","authors":"I. Kawahata, David I. Finkelstein, Kohji Fukunaga","doi":"10.3390/receptors3020009","DOIUrl":"https://doi.org/10.3390/receptors3020009","url":null,"abstract":"Understanding the intricate role of dopamine D1–D5 receptors is pivotal in addressing the challenges posed by the aging global population, as well as by social stress and advancing therapeutic interventions. Central to diverse brain functions such as movement, cognition, motivation, and reward, dopamine receptors are ubiquitously distributed across various brain nuclei. This comprehensive review explores the nuanced functions of each dopamine receptor, D1, D2, D3, D4, and D5, in distinct brain regions, elucidating the alterations witnessed in several neurological and psychiatric disorders. From the substantia nigra and ventral tegmental area, crucial for motor control and reward processing, to the limbic system influencing emotional responses, motivation, and cognitive functions, each brain nucleus reveals a specific involvement of dopamine receptors. In addition, genetic variations in dopamine receptors affect the risk of developing schizophrenia and parkinsonism. The review further investigates the physiological significance and pathogenic impacts of dopamine receptors in critical areas like the prefrontal cortex, hypothalamus, and striatum. By unraveling the complexities of dopamine receptor biology, especially those focused on different brain nuclei, this review provides a foundation for understanding their varied roles in health and disease, which is essential for the development of targeted therapeutic strategies aimed at mitigating the impact of aging and mental health on neurological well-being.","PeriodicalId":507548,"journal":{"name":"Receptors","volume":"13 16","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140711983","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-05DOI: 10.3390/receptors3020008
Lara Toffoli, A. Ditsiou, T. Gagliano
Neuroendocrine tumors (NETs) represent a diverse group of neoplasms originating from neuroendocrine cells, presenting varied clinical behaviors and posing significant challenges in management. This review explores the emerging roles of receptor tyrosine kinases (RTKs) in the pathogenesis and progression of NETs, including vascular endothelial growth factor receptors (VEGFRs), insulin-like growth factor receptors (IGF-1R), RET, epidermal growth factor receptor (EGFR), and ALK. The dysregulation of RTK signaling pathways contributes to key cellular processes such as proliferation, survival, and invasion in NETs. We discuss the potential of targeting RTKs as therapeutic strategies in NETs, with a focus on recent developments in RET inhibitors and the therapeutic implications of RTK alterations.
神经内分泌肿瘤（NET）是一组来源于神经内分泌细胞的多样化肿瘤，临床表现各不相同，给治疗带来了巨大挑战。本综述探讨了受体酪氨酸激酶（RTK）在NET发病和进展过程中的新作用，包括血管内皮生长因子受体（VEGFR）、胰岛素样生长因子受体（IGF-1R）、RET、表皮生长因子受体（EGFR）和ALK。RTK信号通路的失调导致了NET的增殖、存活和侵袭等关键细胞过程。我们讨论了靶向 RTKs 作为 NET 治疗策略的潜力，重点是 RET 抑制剂的最新进展以及 RTK 改变的治疗意义。
{"title":"Exploring Emerging Therapeutic Targets and Opportunities in Neuroendocrine Tumors: Updates on Receptor Tyrosine Kinases","authors":"Lara Toffoli, A. Ditsiou, T. Gagliano","doi":"10.3390/receptors3020008","DOIUrl":"https://doi.org/10.3390/receptors3020008","url":null,"abstract":"Neuroendocrine tumors (NETs) represent a diverse group of neoplasms originating from neuroendocrine cells, presenting varied clinical behaviors and posing significant challenges in management. This review explores the emerging roles of receptor tyrosine kinases (RTKs) in the pathogenesis and progression of NETs, including vascular endothelial growth factor receptors (VEGFRs), insulin-like growth factor receptors (IGF-1R), RET, epidermal growth factor receptor (EGFR), and ALK. The dysregulation of RTK signaling pathways contributes to key cellular processes such as proliferation, survival, and invasion in NETs. We discuss the potential of targeting RTKs as therapeutic strategies in NETs, with a focus on recent developments in RET inhibitors and the therapeutic implications of RTK alterations.","PeriodicalId":507548,"journal":{"name":"Receptors","volume":"6 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140739243","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-03-25DOI: 10.3390/receptors3020007
Miguel Olivas-Aguirre, Cecilia Gutiérrez-Iñiguez, I. Pottosin, Oxana Dobrovinskaya
Recent research has emphasized the potential of natural and synthetic cannabinoids as anticancer agents. Yet it remains unclear whether and in which sense cannabinoids affect the anticancer activity of NK cells, an important branch of anticancer immunity. Similar uncertainty exists regarding NK cells-based immunotherapy. Here we presented an overview of multiple cannabinoid targets as canonical (mainly CB2) and non-canonical receptors, ion channels, transporters, and enzymes, expressed in NK cells, along with underlying molecular mechanisms. Through them, cannabinoids can affect viability, proliferation, migration, cytokine production, and the overall anticancer activity of NK cells. Respective holistic studies are limited, and, mostly, are phenomenological, not linking observed effects with certain molecular targets. Another problem of existing studies is the lack of standardisation, so that diverse cannabinoids at variable concentrations and ways of administration are applied, and often, instead of purified NK cells, the whole lymphocyte population is used. Therefore, there is an urgent need for more focused, systemic, and in-depth studies of the impact of the cannabinoid toolkit on NK cell function, to critically address the compatibility and potential synergies between NK activity and cannabinoid utilization in the realm of anticancer interventions.
最近的研究强调了天然和合成大麻素作为抗癌剂的潜力。然而，大麻素是否以及在何种意义上影响 NK 细胞的抗癌活性（NK 细胞是抗癌免疫的一个重要分支），目前仍不清楚。基于 NK 细胞的免疫疗法也存在类似的不确定性。在此，我们概述了在 NK 细胞中表达的多种大麻素靶点，如规范受体（主要是 CB2）和非规范受体、离子通道、转运体和酶，以及潜在的分子机制。通过它们，大麻素可以影响 NK 细胞的活力、增殖、迁移、细胞因子分泌和整体抗癌活性。相关的整体研究十分有限，而且大多是现象性研究，没有将观察到的效果与某些分子靶点联系起来。现有研究的另一个问题是缺乏标准化，因此使用的大麻素浓度和给药方式各不相同，而且通常使用的不是纯化的 NK 细胞，而是整个淋巴细胞群。因此，迫切需要对大麻素工具包对 NK 细胞功能的影响进行更集中、系统和深入的研究，以批判性地解决 NK 活性和大麻素利用在抗癌干预领域的兼容性和潜在协同作用问题。
{"title":"Molecular Targets for Cannabinoids in Natural Killer Cells: Do They Modulate the Antitumor Activity?","authors":"Miguel Olivas-Aguirre, Cecilia Gutiérrez-Iñiguez, I. Pottosin, Oxana Dobrovinskaya","doi":"10.3390/receptors3020007","DOIUrl":"https://doi.org/10.3390/receptors3020007","url":null,"abstract":"Recent research has emphasized the potential of natural and synthetic cannabinoids as anticancer agents. Yet it remains unclear whether and in which sense cannabinoids affect the anticancer activity of NK cells, an important branch of anticancer immunity. Similar uncertainty exists regarding NK cells-based immunotherapy. Here we presented an overview of multiple cannabinoid targets as canonical (mainly CB2) and non-canonical receptors, ion channels, transporters, and enzymes, expressed in NK cells, along with underlying molecular mechanisms. Through them, cannabinoids can affect viability, proliferation, migration, cytokine production, and the overall anticancer activity of NK cells. Respective holistic studies are limited, and, mostly, are phenomenological, not linking observed effects with certain molecular targets. Another problem of existing studies is the lack of standardisation, so that diverse cannabinoids at variable concentrations and ways of administration are applied, and often, instead of purified NK cells, the whole lymphocyte population is used. Therefore, there is an urgent need for more focused, systemic, and in-depth studies of the impact of the cannabinoid toolkit on NK cell function, to critically address the compatibility and potential synergies between NK activity and cannabinoid utilization in the realm of anticancer interventions.","PeriodicalId":507548,"journal":{"name":"Receptors","volume":"111 27","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140381731","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-03-18DOI: 10.3390/receptors3010006
Jacques Fantini
Receptology, the science of receptors, is a multidimensional field of research which can be dissected into biosynthesis, membrane sorting, ligand binding and signal transduction. Plasma membrane receptors connect the cells with their environment and transmit signals that are translated into biological information. The historical paradigm of ligand–receptor interactions is the lock-and-key model. This model presupposes that both partners have a precise 3D shape that perfectly fits together to form the ligand–receptor complex. However, this simple model suffers from severe limitations due to several levels of simplifications: (i) water molecules and membrane lipids are not considered; (ii) not all ligands have a stable 3D structure; (iii) the ligand-binding pocket of the receptor is often flexible and conformationally rearranged after the initial binding step (induced fit mechanism) and/or subjected to conformational selection by the ligand; (iv) there are signal transduction mechanisms which can be either purely mechanical (conformational change of the receptor induced after binding of the ligand), lipid-assisted (e.g., by raft lipids such as cholesterol or gangliosides), or in some instances of quantic nature (detection of odorant molecules). The aim of the present review is to challenge the old paradigms and present new concepts of membrane receptology that consider the impact of critical parameters such as water molecules, membrane lipids, electrostatic surface potential and quantum mechanisms.
{"title":"Fundamental Mechanisms in Membrane Receptology: Old Paradigms, New Concepts and Perspectives","authors":"Jacques Fantini","doi":"10.3390/receptors3010006","DOIUrl":"https://doi.org/10.3390/receptors3010006","url":null,"abstract":"Receptology, the science of receptors, is a multidimensional field of research which can be dissected into biosynthesis, membrane sorting, ligand binding and signal transduction. Plasma membrane receptors connect the cells with their environment and transmit signals that are translated into biological information. The historical paradigm of ligand–receptor interactions is the lock-and-key model. This model presupposes that both partners have a precise 3D shape that perfectly fits together to form the ligand–receptor complex. However, this simple model suffers from severe limitations due to several levels of simplifications: (i) water molecules and membrane lipids are not considered; (ii) not all ligands have a stable 3D structure; (iii) the ligand-binding pocket of the receptor is often flexible and conformationally rearranged after the initial binding step (induced fit mechanism) and/or subjected to conformational selection by the ligand; (iv) there are signal transduction mechanisms which can be either purely mechanical (conformational change of the receptor induced after binding of the ligand), lipid-assisted (e.g., by raft lipids such as cholesterol or gangliosides), or in some instances of quantic nature (detection of odorant molecules). The aim of the present review is to challenge the old paradigms and present new concepts of membrane receptology that consider the impact of critical parameters such as water molecules, membrane lipids, electrostatic surface potential and quantum mechanisms.","PeriodicalId":507548,"journal":{"name":"Receptors","volume":"32 8","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140234842","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：