RESUMO
Ca2+/cAMP ratio could serve as an inflammatory index for diseases like hyp-ertension, diabetes, and coronavirus disease 2019.
Assuntos
Cálcio , AMP Cíclico , Inflamação , Humanos , AMP Cíclico/análise , Cálcio/análise , Inflamação/diagnósticoAssuntos
COVID-19 , Transtornos Mentais , Cálcio , AMP Cíclico , Humanos , Transtornos Mentais/diagnóstico , Transdução de SinaisRESUMO
BACKGROUND: The hypothesis that a dyshomeostasis of Ca2+ increases the incidence of dementia has been established. Several discoveries have emphasized the concept that a decrease in the excess of Ca2+ could be an interesting pharmacological target to alleviate dementia symptoms. Aging along with a healthy brain can be supported by daily exercise, self-control in caloric ingestion, and participation in intellectually challenging events. These lifestyle factors may alleviate the excess of Ca2+ resulting from a Ca2+ dyshomeostasis. Curiously, epidemiological and clinical studies have also reported a clinical relationship between hypertension, diabetes, and other inflammatory processes, and a higher risk of cognition decline. Considering the cumulative data from the scientific literature, including data of high evidence such as meta-analysis and systematic reviews, we can now link a Ca2+ dyshomeostasis as an upstream factor for hypertension, diabetes and other inflammatory processes, and dementia. Several reports have also indicated that increasing cAMP levels may induce neuroprotective outcomes, thus alleviating dementia symptoms. METHODS: With these concepts in mind, we found that the pharmacological manipulation of Ca2+/cAMP signalling could be a novel plausible target to treat dementia. This article puts together fundamental concepts and current therapies to treat dementia, including novel therapeutics coming from the pharmacological manipulation of Ca2+/cAMP signalling. RESULTS: Then, combined with improvements in the lifestyle issues, these novel therapeutics may allow sustained improvements in the life quality of age-related neurological patients. CONCLUSIONS: In addition, considering coronavirus disease 2019 (COVID-19) is a rapidly evolving field, this article also reviewed recent reports about Ca2+ channel blockers' role in restoring Ca2+ signalling disruption due to COVID-19. Finally, this article also presents a timeline of the major events in Ca2+/cAMP signaling.
Assuntos
Tratamento Farmacológico da COVID-19 , Demência , Diabetes Mellitus , Hipertensão , AMP Cíclico/uso terapêutico , Demência/tratamento farmacológico , Diabetes Mellitus/tratamento farmacológico , HumanosRESUMO
BACKGROUND: The hypothesis that hypertension is clinically associated with an enhanced risk of developing cancer has been highlighted. However, the working principles involved in this link are still under intensive discussion. A correlation among inflammation, hypertension, and cancer could accurately describe the clinical link between these diseases. In addition, dyshomeostasis of Ca2+ has been considered to be involved in both cancer and hypertension, and inflammation. There is a strong link between Ca2+ signalling, e.g. enhanced Ca2+ signals, and inflammatory outcomes. cAMP also modulates pro- and anti-inflammatory outcomes; pharmaceuticals, which increase intracellular cAMP levels, can decrease the production of proinflammatory mediators and enhance the production of antiinflammatory outcomes. OBJECTIVE: This article highlights the participation of Ca2+/cAMP signalling in the clinical association among inflammation, hypertension, and an enhanced risk for the development of cancer. In addition, considering that research on coronavirus disease 2019 (COVID-19) is a rapidly evolving field, this article also reviews recent reports related to the role of Ca2+ channel blockers in restoring Ca2+ signalling disruption due to COVID-19, including the relationship among COVID-19, cancer, and hypertension. CONCLUSION: An understanding of the association among these diseases could expand current pharmacotherapy, involving Ca2+ channel blockers and pharmaceuticals that facilitate a rise in cAMP levels.
Assuntos
COVID-19 , Hipertensão , Neoplasias , COVID-19/complicações , Cálcio/metabolismo , Sinalização do Cálcio , AMP Cíclico/metabolismo , AMP Cíclico/uso terapêutico , Humanos , Hipertensão/complicações , Hipertensão/tratamento farmacológico , Inflamação , Preparações FarmacêuticasRESUMO
A link between inflammatory diseases, e.g., epilepsy, dementia, diabetes, and COVID-19, has been established. For instance, observational studies involving several individuals reported that people with epilepsy show an enhanced incidence of manifesting dysfunctions related to cognition, e.g., dementia, while people with dementia have a higher incidence of manifesting epilepsy, thus an evident bidirectional relationship between epilepsy and dementia might occur. In addition, epilepsy commonly cooccurs in patients with diabetes, indicating an association between these two disorders. Intriguingly, some reports have also observed a poor prognosis of people with both diabetes and COVID-19. It is recognized that a dyshomeostasis of both Ca2+ and cAMP signalling pathways could be a molecular connection for these disorders. Therefore, clarifying this clinical relationship among epilepsy, dementia, diabetes, and COVID-19 may outcome in novel hypotheses for identifying the etiology of these disorders.
Assuntos
COVID-19 , Demência , Diabetes Mellitus , Epilepsia , COVID-19/complicações , AMP Cíclico/metabolismo , Diabetes Mellitus/epidemiologia , Diabetes Mellitus/metabolismo , Humanos , Doenças NeuroinflamatóriasRESUMO
A large amount of evidence has supported a clinical link between diabetes and inflammatory diseases, e.g., cancer, dementia, and hypertension. In addition, it is also suggested that dysregulations related to Ca2+ signaling could link these diseases, in addition to 3'-5'-cyclic adenosine monophosphate (cAMP) signaling pathways. Thus, revealing this interplay between diabetes and inflammatory diseases may provide novel insights into the pathogenesis of these diseases. Publications involving signaling pathways related to Ca2+ and cAMP, inflammation, diabetes, dementia, cancer, and hypertension (alone or combined) were collected by searching PubMed and EMBASE. Both signaling pathways, Ca2+ and cAMP signaling, control the release of neurotransmitters and hormones, in addition to neurodegeneration, and tumor growth. Furthermore, there is a clear relationship between Ca2+ signaling, e.g., increased Ca2+ signals, and inflammatory responses. cAMP also regulates pro- and anti-inflammatory responses. Due to the experience of our group in this field, this article discusses the role of Ca2+ and cAMP signaling in the correlation between diabetes and inflammatory diseases, including its pharmacological implications. As a novelty, this article also includes: (1) A timeline of the major events in Ca2+/cAMP signaling; and (2) As coronavirus disease 2019 (COVID-19) is an emerging and rapidly evolving situation, this article also discusses recent reports on the role of Ca2+ channel blockers for preventing Ca2+ signaling disruption due to COVID-19, including the correlation between COVID-19 and diabetes.
RESUMO
BACKGROUND: Robust evidence has described that Parkinson´s disease (PD) is associated with an increased risk for developing epileptic seizures. In fact, an interplay between PD and epilepsy has been of interest for many years. An emerging hypothesis is that inflammation could link both diseases. OBJECTIVE: Bearing in mind the experience of our group in the field of Ca2+/cAMP signalling pathways, this article discussed, beyond inflammation, the role of these signalling pathways in this link between PD and epilepsy. METHODS: Publications involving Ca2+/cAMP signalling pathways, PD, and epilepsy (alone or combined) were collected by searching PubMed and EMBASE. RESULTS: The comprehension of the interplay between PD and epilepsy could improve the drug therapy. In addition, a Ca2+ signalling dyshomeostasis due to Coronavirus disease 2019 (COVID-19), an emerging and rapidly evolving situation, has been reported. CONCLUSION: Thus, this article also debated recent findings about therapeutics involving Ca2+ channel blockers for preventing Ca2+ signalling dyshomeostasis due to COVID-19, including the correlation among COVID-19, epilepsy, and PD.
Assuntos
Sinalização do Cálcio , AMP Cíclico , Epilepsia/complicações , Inflamação/complicações , Doença de Parkinson/complicações , Transdução de Sinais , COVID-19/complicações , Bloqueadores dos Canais de Cálcio/uso terapêutico , Epilepsia/fisiopatologia , Humanos , Inflamação/fisiopatologia , Doença de Parkinson/fisiopatologiaRESUMO
BACKGROUND: A large amount of evidence has described that asthma may be associated with a high epilepsy risk, and epilepsy may be linked with high asthma risk, especially among children and individuals in their 30s. Curiously, asthma has also been associated with an increased risk for schizophrenia. Most interestingly, a bidirectional link between schizophrenia and epilepsy has also been established and has been of interest for many years. OBJECTIVE: Bearing in mind the experience of our group in the field of Ca2+/cAMP signalling pathways, this article discussed, beyond inflammation, the role of these signalling pathways in this link among epilepsy, asthma, and schizophrenia. METHODS: Publications involving these signalling pathways, asthma, epilepsy, and schizophrenia (alone or combined) were collected by searching PubMed and EMBASE. RESULTS AND CONCLUSION: There is a clear relationship between Ca2+ signalling, e.g. increased Ca2+ signals and inflammatory responses. In addition to Ca2+, cAMP regulates pro- and anti-inflammatory responses. Then, beyond inflammation, the comprehension of the link among epilepsy, asthma, and schizophrenia could improve the drug therapy.
Assuntos
Asma , Epilepsia , Esquizofrenia , Asma/metabolismo , Sinalização do Cálcio/fisiologia , Criança , AMP Cíclico/metabolismo , Humanos , InflamaçãoRESUMO
Asthma has been associated with an increased risk for developing schizophrenia. In addition, schizophrenia has been associated with an increased risk for developing type 2 diabetes mellitus, resulting in an elevated cardiovascular risk and in a limited life expectancy. It is well discussed that dysregulations related to Ca2+ signaling could link these diseases, in addition to cAMP signaling pathways. Thus, revealing this interplay among schizophrenia, diabetes, and asthma may provide novel insights into the pathogenesis of these diseases. Publications involving Ca2+ and cAMP signaling pathways, schizophrenia, diabetes, and asthma (alone or combined) were collected by searching PubMed and EMBASE. Both Ca2+ and cAMP signaling pathways (Ca2+/cAMP signaling) control the release of neurotransmitters and hormones, in addition to airway smooth muscle contractility, then dysregulations of these cellular processes may be involved in these diseases. Taking into consideration, the experience of our group in this field, this narrative review debated the involvement of Ca2+/cAMP signaling in this link among schizophrenia, diabetes, and asthma, including its pharmacological implications.
RESUMO
BACKGROUND: Considering a consistent body of evidence has been showing that schizophrenia patients have had an increased risk of developing dementia. The hypothesis that dementia and schizophrenia share a complex link, is emerging. It is highly discussed that dysregulations related to Ca2+ signalling, e.g., an increase of the intracellular concentration of Ca2+, could link both diseases, in addition to cAMP signalling pathways. OBJECTIVE: Thus, revealing this interplay between schizophrenia and dementia may provide novel insights into the pathogenesis of these diseases. METHODS: Publications involving Ca2+ and cAMP signalling pathways, dementia and schizophrenia (alone or combined) were collected by searching PubMed and EMBASE. RESULTS: Both Ca2+ and cAMP signalling pathways (Ca2+/cAMP signalling) control the release of neurotransmitters/ hormones and neuronal death, and dysregulations of these cellular processes may be involved in both diseases. CONCLUSION: Bearing in mind the experience of our group in this field, this article debated the involvement of Ca2+/cAMP signalling in this link between schizophrenia and dementia, including its pharmacological implications.
Assuntos
Demência , Esquizofrenia , Cálcio , AMP Cíclico , Humanos , Esquizofrenia/tratamento farmacológico , Transdução de SinaisRESUMO
BACKGROUND: The interactions between Alzheimer's Disease (AD) and major depression can be translated into clinical data showing that depressive patients have had an enhanced risk for developing AD (later in life). The cellular mechanisms involved in these interactions remain under intensive debate in the literature. In addition, the role of a Ca2+ homeostasis dysregulation in the pathogenesis of neurodegenerative diseases, like AD, and major depression has been under intensive discussion. OBJECTIVE: Thus, revealing the interplay between AD and major depression may provide novel insights into the pathogenesis of these diseases. METHODS: Publications involving Ca2+ signalling pathways, AD, and major depression (alone or combined) were collected by searching multiple databases to find the maximum number of relevant citations (using a search strategy with high sensitivity for studies of etiology). RESULTS: Ca2+ Channel Blockers (CCBs), classically prescribed for hypertensive patients, have been demonstrating neuroprotective effects, such as decreasing the incidence of AD in hypertensive patients, including alleviating major depression symptoms. A mechanism under debate is focused on the restoration of the Ca2+ homeostasis. Indeed, previous studies of our own have correlated Ca2+ and cAMP signalling pathways (Ca2+/cAMP signalling) in controlling both the neurotransmitter release and neuronal death. These studies also observed that CCBs can affect Ca2+/cAMP signalling. CONCLUSION: This review discussed the plausible role of Ca2+/cAMP signalling in the neuroprotective effects of CCBs, including the participation of Ca2+/cAMP signalling in the interactions between major depression and AD. Considering both AD and major depression have become highly prevalent medical problems in the world, the comprehension of the interactions between these diseases could improve drug development.
Assuntos
Doença de Alzheimer/tratamento farmacológico , Bloqueadores dos Canais de Cálcio/farmacologia , Transtorno Depressivo Maior/tratamento farmacológico , Doença de Alzheimer/fisiopatologia , Cálcio/metabolismo , Sinalização do Cálcio/efeitos dos fármacos , AMP Cíclico/metabolismo , Transtorno Depressivo Maior/fisiopatologia , Humanos , Fármacos Neuroprotetores/farmacologia , Fatores de RiscoRESUMO
Limitations on the pharmacotherapy and a high prevalence worldwide are critical issues related to depression and cancer. It has been discussed that a dysregulation of intracellular Ca2+ homeostasis is involved in the pathogenesis of both these diseases. In addition, depression raises the risk of cancer incidence. Consistent data support the concept that depression is an independent risk issue for cancer. However, the cellular mechanisms involved in this link between depression and cancer remain uncertain. Considering our previous reports about Ca2+ and cAMP signalling pathways (Ca2+/cAMP signalling), I herein discussed the putative contribution of Ca2+/cAMP signalling in this link between depression and cancer. Moreover, it is important to take depression into account during the process of prevention and treatment of cancer.
Assuntos
Cálcio/metabolismo , AMP Cíclico/metabolismo , Depressão/metabolismo , Neoplasias/metabolismo , Animais , Humanos , Transdução de SinaisRESUMO
BACKGROUND: Parkinson´s disease (PD) and depression have an interplay at multiple cellular levels, a phenomenon which is translated into clinical data showing that depressive patients presented an enhanced risk for developing PD. The pathogenesis of both diseases is under intensive debate as correlated to dysregulations related to Ca2+ signaling. OBJECTIVE: Then, revealing this interplay between these diseases may provide novel insights into the pathogenesis of them. METHODS: Publications involving Ca2+ signaling, PD and depression (alone or combined) were collected by searching PubMed and EMBASE. RESULTS: Not surprisingly, calcium (Ca2+) channel blockers (CCBs), classical antihypertensive medicines, have been demonstrated off-label effects, such as alleviating both PD and depression symptoms. DISCUSSION: A mechanism under debate for the antiparkinsonism and antidepressant effects associated to CCBs is focused on the restoration of Ca2+ signaling dysregulations. In addition, previous studies have observed that CCBs can affect Ca2+/cAMP signaling. CONCLUSION: Thus, this article discussed the role of Ca2+/cAMP signaling in the interplay between depression and PD, including the implications for the pharmacotherapy involving CCBs.
Assuntos
Antidepressivos/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Bloqueadores dos Canais de Cálcio/uso terapêutico , Sinalização do Cálcio/efeitos dos fármacos , Depressão/tratamento farmacológico , Fármacos Neuroprotetores/uso terapêutico , Doença de Parkinson/tratamento farmacológico , Encéfalo/metabolismo , Encéfalo/patologia , Cálcio/metabolismo , AMP Cíclico/metabolismo , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/genética , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Proteínas Quinases Dependentes de AMP Cíclico/genética , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Depressão/complicações , Depressão/genética , Depressão/metabolismo , Regulação da Expressão Gênica , Humanos , Terapia de Alvo Molecular/métodos , Doença de Parkinson/complicações , Doença de Parkinson/genética , Doença de Parkinson/metabolismoRESUMO
BACKGROUND: A correlation between cognitive dysfunctions and brain insulin resistance has been established by several clinical and experimental studies. Consistent data support that people diagnosed with brain insulin resistance, resulted from diabetes, have shown an increased risk of presenting cognitive dysfunctions, clinical signs of dementia and depression, then speculating a role of dysregulations related to insulin signalling in these diseases. Furthermore, it is currently discussed that Ca2+ signalling, and its dysregulations, may be a factor which could correlate with brain insulin resistance and cognitive dysfunctions. OBJECTIVE: Following this, revealing this interplay between these diseases may provide novel insights into the pathogenesis of such diseases. METHODS: Publications covering topics such as Ca2+ signalling, diabetes, depression and dementia (alone or combined) were collected by searching PubMed and EMBASE. RESULTS: The controlling of both neurotransmitters/hormones release and neuronal death could be achieved through modulating Ca2+ and cAMP signalling pathways (Ca2+/cAMP signalling). CONCLUSION: Taking into account our previous reports on Ca2+/cAMP signalling, and considering a limited discussion in the literature on the role of Ca2+/cAMP signalling in the link between cognitive dysfunctions and brain insulin resistance, this article has comprehensively discussed the role of these signalling pathways in this link (between cognitive dysfunctions and brain insulin resistance).
Assuntos
Encéfalo/metabolismo , Sinalização do Cálcio/fisiologia , Disfunção Cognitiva/metabolismo , AMP Cíclico/metabolismo , Sistemas de Liberação de Medicamentos/métodos , Resistência à Insulina/fisiologia , Animais , Encéfalo/efeitos dos fármacos , Sinalização do Cálcio/efeitos dos fármacos , Disfunção Cognitiva/tratamento farmacológico , Diabetes Mellitus/tratamento farmacológico , Diabetes Mellitus/metabolismo , Humanos , Hipoglicemiantes/administração & dosagemRESUMO
BACKGROUND: Depression and hypertension are medical problems both with clearly restricted pharmacotherapies, along with a high prevalence around the world. In fact, an intensive discussion in the field is that a dysregulation of the intracellular Ca2+ homeostasis (e.g. excess of intracellular Ca2+) contributes to the pathogenesis of both hypertension and depression. Furthermore, depression rises the risk of hypertension incidence. Indeed, several data support the concept that depression is an independent risk issue for hypertension. CONCLUSION: Then, which are the possible cellular mechanisms involved in this link between depression and hypertension? Considering our previous reports about the Ca2+ and cAMP signalling pathways (Ca2+/cAMP signalling), in this review I have discussed the virtual involvement of the Ca2+/cAMP signalling in this link (between depression and hypertension). Then, it is important to consider depression into account during the process of prevention, and treatment, of hypertension.
Assuntos
Pressão Sanguínea , Sinalização do Cálcio , AMP Cíclico/metabolismo , Depressão/metabolismo , Hipertensão/metabolismo , Antidepressivos/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Bloqueadores dos Canais de Cálcio/uso terapêutico , Sinalização do Cálcio/efeitos dos fármacos , Depressão/tratamento farmacológico , Depressão/epidemiologia , Depressão/fisiopatologia , Humanos , Hipertensão/tratamento farmacológico , Hipertensão/epidemiologia , Hipertensão/fisiopatologia , Incidência , Fatores de Risco , Transdução de SinaisRESUMO
OBJECTIVE: Asthma is correlated with a higher risk of manifesting other diseases, including hypertension, diabetes, obesity, psychiatric and neurological diseases, and cancer. Therefore, revealing this interplay between asthma and these illnesses may provide novel insights into their pathogenesis. RESULTS: It is highly debated that dysregulation of Ca2+ homeostasis is involved in the pathogenesis of these maladies. Not surprisingly, calcium (Ca2+) channel blockers (CCBs), classically used as antihypertensive medicines, have been demonstrating off-label effects such as alleviating asthma symptoms, in addition to antidiabetic, antiobesity, anticancer and antineurodegenerative effects. Our studies about Ca2+/cAMP signalling may shed some new light on this field. CONCLUSION: Thus, considering that asthma and associated illnesses such as hypertension, diabetes, obesity, cancer and neurodegenerative diseases have become highly prevalent medical problems in the world, the comprehension of this interplay between asthma and other disorders could improve drug therapy.
Assuntos
Asma/epidemiologia , Asma/metabolismo , Sinalização do Cálcio/fisiologia , AMP Cíclico/metabolismo , Animais , Comorbidade , Diabetes Mellitus/epidemiologia , Diabetes Mellitus/metabolismo , Humanos , Hipertensão/epidemiologia , Hipertensão/metabolismo , Neoplasias/epidemiologia , Neoplasias/metabolismo , Doenças Neurodegenerativas/epidemiologia , Doenças Neurodegenerativas/metabolismo , Fatores de RiscoRESUMO
BACKGROUND: A link between diabetes and Parkinson´s disease (PD) has been established by several reports. Consistent data report that people diagnosed with diabetes have demonstrated an enhanced risk of manifesting PD in their lifetime. The working principles involved in this link have been extensively discussed. Over the last decade, diabetes has been reported to be correlated with an increased risk of dementia, suggesting a potential role of diabetes, or insulin signalling dysregulations, in neurodegeneration. In addition, it is nowadays highly debated that dysregulations related to Ca2+ signalling may be an upstream issue which could also link diabetes and PD. Ca2+ and cAMP signalling pathways (Ca2+/cAMP signalling) control both the neurotransmitters/hormones release and neuronal death. CONCLUSION: Considering our previous reports about Ca2+/cAMP signalling, the putative contribution of Ca2+/cAMP signalling in this link (between diabetes and PD) is discussed in this paper.
Assuntos
Cálcio/fisiologia , AMP Cíclico/fisiologia , Diabetes Mellitus/fisiopatologia , Doença de Parkinson/fisiopatologia , Transdução de Sinais/fisiologia , Humanos , Doença de Parkinson/etiologiaRESUMO
BACKGROUND: Hypertension, diabetes and neurodegenerative diseases are among the most prevalent medical problems around the world, costing millions of dollars to the medical health systems. Indeed, hypertension has been associated with higher risk for decline of cognition, as evidenced in patients with Alzheimer´s disease (AD). Furthermore, there is a clear relationship between hypertension and diabetes, reflecting substantial overlap in their etiology. Calcium (Ca2+) channel blockers (CCBs) have been classically prescribed for treating hypertension because of their mechanism of action due to reducing the influx of Ca2+ into the smooth muscles cells. In addition, many clinical and experimental studies have been demonstrating pleiotropic effects for CCBs. For instance, in hypertensive patients treated with CCBs, it can be observed lower incidence of neurodegenerative diseases such as AD. The virtual mechanism of action could be attributed to a restoration and maintenance of Ca2+ homeostasis, which is dysregulated in the neurodegenerative diseases, including also a reduction of neuronal apoptosis as part of these CCBs pleiotropic effects. Similarly, in hypertensive patients treated with CCBs, it can be observed an improvement of diabetes status such as glycemic control. A possible mechanism of action under debate could be attributed to a restoration of insulin secretion, then achieving glycemic control, and reduction of pancreatic ß-cell apoptosis. CONCLUSION: Considering the discovery of our group entitled "calcium paradox" due to Ca2+/cAMP signalling interaction, in this review I discussed the virtual involvement of this interaction in the pleiotropic effects of CCBs, including the possible role of the Ca2+/cAMP signalling interaction in the association between hypertension and higher risk for the decline of cognition, and diabetes.