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
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: 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
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.