RESUMO
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: 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: 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
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: 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.