Leandro Bueno Bergantin

Universidade Federal de São Paulo | UNIFESP · Departamento de Farmacologia

Ca2+/cAMP ratio could serve as an inflammatory index for diseases like hyp-ertension, diabetes, and coronavirus disease 2019.

Background The hypothesis that a dyshomeostasis of Ca2+ increases the incidence of dementia has been established. In fact, several discoveries have emphasized the concept that a decrease of 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 exe...

Background The hypothesis that hypertension is clinically associated with an enhanced risk for 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 diseas...

Background A link between inflammatory diseases, e.g., epilepsy, dementia, diabetes, and COVID-19, has been established. For instance, observational studies with several individuals established that people with epilepsy have shown an enhanced incidence of manifesting dysfunctions related to cognition, e.g., dementia, while people with dementia have...

Abstract: 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 o...

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...

Dementia, diabetes, and hypertension are considered huge medical problems around the world, costing many millions of dollars to the medical health systems. Curiously, hypertension has been clinically linked with a higher risk for decline of cognition, as shown in dementia patients. In addition, there is a clear clinical association between hyperten...

Background: A large amount of evidence has described that asthma may be associated with a high epilepsy risk, and epilepsy may be linked with a 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 betwee...

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 th...

Obesity and depression are serious public health problems and cause death in the world. In this article, we will study the concept of depreobesity that explains the depression in the context of obesity and vice versa. We will review whether animals can be used to understand the interrelationship between obesity and depression. We will propose saliv...

A link between depression and obesity has been established by several reports. Consistent data support a bidirectional link between depression and obesity, e.g. obese people have demonstrated an increased risk of developing depression in their lifetime, whereas depressed people have shown an increased risk of becoming obese. An intensive debate in...

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 could link both diseases, in addition to cAMP sig...

Limitations on the pharmacotherapy and a high prevalence worldwide are critical issues related to depression and cancer. It is highly discussed in the field that a dysregulation of intracellular Ca2+ homeostasis is involved in the pathogenesis of both diseases. In addition, depression rises the risk of cancer incidence. Consistent data support the...

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 literature. In addition, the role of a Ca+2 home...

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....

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 An...

Clinically characterized by motor dysfunctions such as bradykinesia, rigidity, and resting tremor, Parkinson's disease (PD) is considered the second most common neurodegenerative disease in developed countries. Although these dysfunctions result from a degeneration and death of dopamine (DA) neurons in the substantia nigra (SN), PD etiology remains...

Clinically characterized by motor dysfunctions such as bradykinesia, rigidity, and resting tremor, Parkinson's disease (PD) is considered as the second most common neurodegenerative disease in developed countries. Although these dysfunctions result from a degeneration and death of dopamine (DA) neurons in the substantia nigra (SN), the PD etiology...

Objective: Asthma is correlated with a higher risk of manifesting other diseases, including hypertension, diabetes, obesity, psychiatric and neurological diseases, and cancer. Then, revealing this interplay between asthma and these illnesses may provide novel insights into the pathogenesis of them. Results: It is highly debated that a dysregulatio...

Background: A link between diabetes and Parkinson´s disease (PD) has been established by several reports. Consistent data support 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 highly discussed. Over the last decade, diabetes has been...

Youtube: https://www.youtube.com/watch?v=dG_jyV0VaEI&t=55s

The incidence of both cancer and diabetes is dramatically increasing in worldwide population, costing many millions from governments into expenditures related to medical health systems. Diabetes has been clinically linked to an increased risk for developing several types of cancer. The cellular mechanisms involved in this link are still under inten...

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 hypertensi...

Many reports have been demonstrating off-label effects for calcium (Ca2+) channel blockers (CCBs), for example: patients medicated with CCBs have had an improvement of their diabetes status (control of glycemia), along with an improvement of both depression symptoms and cognitive function. Indeed, diabetes and depression are medical problems both w...

The evidences that a dysregulation of the intracellular Ca2+ homeostasis increases the incidence of the neurodegenerative diseases, such as Alzheimer´s disease (AD), have been increasing. Thus, several findings have been reinforcing the concept that a reduction of a cytosolic Ca2+ excess, achieved due to the L-type Ca2+ channel blockers (CCBs), cou...

This book extends the original concept of the “calcium paradox” discovery, herein compiling more than 300 references in the field of calcium ion (Ca2+/cAMP) signalling pathways, neurotransmission and neurodegeneration, and neurological and psychiatric diseases. In this second edition, novel illustrations and tables (highlighting current medicines f...

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 i...

The incidence of cancer and hypertension is dramatically increasing in worldwide population, costing millions and millions from governments into expenditures related to the medical health systems. Interestingly, hypertension has been clinically linked to an increased risk for developing cancer. However, the mechanisms involved in this possible link...

Due to the involvement of the imbalance of neuronal Ca2+ homeostasis in the pathogenesis of several neurodegener-ative diseases, the use of drugs to prevent or attenuate this imbalance emerged as a new therapeutic strategy for treating these diseases. Thus, our discovery of the involvement of the interaction between intracellular signaling pathways...

This editorial brings insights for the clinical link between Alzheimer´s disease and Depression through the Ca2+/cAMP signaling interaction.

My current field of research involves the study of the interaction between Ca 2+ and cAMP signalling pathways, including its role in neurological disorders. The scientific literature now clearly accepts this interaction as a fundamental cellular process, which is also involved in synaptic transmission mainly by controlling neurotransmitter release...

This editorial brings the expectations, and my impressions, for the field of neurological and psychiatric diseases in 2018.

Editorial: The vascular smooth muscle tone must be well-controlled to assure a perfect regulation of blood pressure. In this arena, we have two important intracellular messengers: Ca 2+ and cAMP. Classically, the rise of intracellular Ca 2+ within vascular smooth muscle cells starts a well-organized symphony which reaches into muscle contraction. N...

Alzheimer’s disease (AD) is the most common cause of progressive dementia in the elderly. It is characterized by a progressive and irreversible loss of cognitive abilities and formation of senile plaques, composed mainly of amyloid β (Aβ), and neurofibrillary tangles (NFTs), composed of tau protein, in the hippocampus and cortex of afflicted humans...

https://www.frontiersin.org/articles/10.3389/fnagi.2018.00004/full

Our group has been pioneering in exploring that the pharmacological handling of Ca 2+/ cAMP signalling interaction could be a better therapeutic method for increasing neurotransmission in psychiatric disorders, and stimulating neuroprotection for combating neurodegenerative diseases, such as Alzheimer´s disease. Indeed, Ca 2+ is a classic intracell...

Editorial: Our discovery that the interaction between Ca 2+ and cAMP signalling pathways plays a role in the synaptic transmission, including protection against neurodegeneration, has supported thoughtful ideas about the neurobiology of the neurological disorders, opening a large pathway for the improvement of new pharmacological approaches for han...

Since 70´s, the sympathetic hyperactivity due to increment of catecholamine plasma levels is the main adverse effect reported by hypertensive patients that use L-type Ca 2+ channel blockers (CCBs). Our discovery of the involvement of interaction between the intracellular signalling pathways mediated by Ca 2+ and cAMP (Ca 2+ /cAMP interaction) revea...

Alzheimer's disease (AD) is a debilitating neuropsychiatric disorder characterized by the multifaceted decline in cognitive and behavioral functions. Due to the multifaceted nature of AD pathology and our limited understanding on its etiology, AD is difficult to be treated with currently available pharmaceuticals. Then, new therapeutic strategies f...

About 4 years ago, we showed that the paradoxical effects (sympathetic hyperactivity) induced by L-type voltage-activated Ca 2+ channels (VACC) blockers, named by us "calcium paradox" phenomenon, were potentiated by drugs which increase cytosolic cAMP concentration ([cAMP] c-enhancers), for example rolipram, IBMX and forskolin, indicating that the...

The solution for the so-called "calcium paradox" has been revealed 4 years ago, when we demonstrated the involvement of the interaction between Ca 2+ and cAMP signalling pathways (Ca 2+ /cAMP signalling interaction) in this enigma. The "calcium paradox" emerged 4 decades ago, when numerous clinical studies have concluded that prescription of L-type...

"Science is not always linear! Imagine this scenario: The PhD researcher and his supervisor are formulating their experiment. During the experiment course, there is on the bench a residual solution containing Verapamil, an L-type Ca2+ channel blocker (CCB). In a relapse, the PhD researcher decides to add this solution in an isolated smooth muscle p...

Caricati-Neto A, Bergantin LB. Huntington´s disease and the interaction between Ca 2+ and cAMP signaling pathways. J Pharmacol Res December-2017;1(1):17-24. Huntington disease (HD) is a neurodegenerative disease known by progressive motor, behavioral, and cognitive decline that culminates in the death. HD therapy is yet unsatisfactory. Chorea and p...

It is well recognized that an imbalance of intracellular Ca 2+ homeostasis contributes to the pathogenesis of neurodegenerative diseases, such as Alzheimer's (AD). Therefore, regulation of intracellular Ca 2+ homeostasis may represent a new target for treatment of this disease. Our recent discovery of the participation of the interaction between in...

Cancer is a major public health problem and the second leading cause of mortality around the world. Antitumor immunotherapy using monoclonal antibodies is considered selective and efficient in the treatment of different types of tumors, but its cost and toxic effects limit its application. Many tumor microenvironments, including lymphoma and carcin...

According to a 2015 United Nations report on world population ageing, the number of people aged 60, and older, worldwide can double in the next 35 years, reaching almost 2.1 billion people. The growing increment in the life expectancy of the world's population has increased the concern about the age-related neurodegenerative diseases, such as Alzhe...

The pharmaceutical intervention on the interaction between intracellular signaling pathways mediated by Ca2+ and cAMP (Ca2+/cAMP signaling interaction) could bring important benefits for combating neurodegeneration and diseases related to aging. This discovery emerged from classical neurotransmission studies using rodent vas deferens as a model. Fr...

The technique of fluorescence microscopy has become an essential tool in the biomedical sciences. In all living cells, cellular, physiological, and pathological phenomena are accompanied by ionic changes. Then, the development of this technique that allows the measurement of intracellular ion activities has contributed substantially to understandin...

Background: Acute myocardial infarction (AMI) is characterized by ischemic lesions that severely compromise the cardiac structure/function, besides the survival of mammals. Although conventional therapy uses cardiac reperfusion, this procedure increases the cardiac damage caused by ischemia. Methods: Adult male Wistar rats (NWR) were anesthetized,...

This editorial highlights the relevance of interfering in cancer cell progression through the pharmacological manipulation on the cell metabolism of cyclic nucleotides such as cAMP, and on the intracellular Ca2+ signaling, which may avail the reduction of toxic effects promoted by chemotherapy, radiotherapy and immunotherapy, thus decreasing the in...

To study cardioprotective drugs, we developed a simple and efficient methodology to evaluate effects of drugs on cardiac electrical activity using electrocardiogram (ECG) in rats submitted to cardiac ischemia-reperfusion (I/R). Using adult male Wistar rats (14-16-week-old) anesthetized (urethane 1.25 g/kg, i.p.) and kept under mechanical ventilatio...

Introdução: A hipertensão arterial é um dos fatores de risco para doenças cardiovasculares, estando diretamente associada ao elevado consumo de sódio. Objetivo: Avaliar os níveis de marcadores de lesão hepática, renal e cardíaca em ratos hipertensos comparados aos seus controles normotensos, tratados com um salgante isento de sódio, água ou NaCl. M...

It is well established that an imbalance of intracellular Ca 2+ homeostasis contributes to the disease progression of neurodegenerative illnesses related to aging, such as Alzheimer's disease (AD). Therefore, regulation of intracellular Ca 2+ homeostasis may represent a new strategy for treatment of this disease. Our recent discovery of the involve...

Amyotrophic lateral sclerosis (ALS) is a devastating neurological disease characterised by progressive muscular paralysis reflecting selective degeneration and death of motor neurons in the primary motor cortex, brainstem and spinal cord. Several evidences suggest the involvement of the imbalance of the intracellular Ca2+ homeostasis in the death o...

It has been almost 4 years since we revealed the solution for the enigma of the so-called “calcium paradox”. Our discovery of the involvement of Ca2+/cAMP signaling interaction in the regulation of neurotransmitter release, and neuro protection, was clearly a serendipitous discovery. It has produced new avenues in the understanding of the cellular...

Cell signaling is a crucial event for the survival and progress of normal cellular functions. However, mutations of certain genes can lead to the emerging of cancer cells, which can use these signaling mechanisms for their survival, growth and dissemination. Among these mechanisms, we highlight the role of cyclic nucleotides such as cAMP, and Ca2+...

An emerging word in biomedical research nowadays is the " translational research ". Basically, " translating " current knowledge from basic science to approaches for treating human disease-from bench to bedside-is the main concept. Our discovery entitled " calcium paradox " fits properly in this main concept. The enigma of the " calcium paradox " i...

The interaction between intracellular signalling pathways mediated by Ca2+ and cAMP (Ca2+/cAMP signalling interaction) is now well-accepted as a vital cellular process for mammalians. In the neuroscience field, it has opened a new avenue for the drug development more effective, and safer, for the treatment of Alzheimer´s and neurodegenerative disea...

Clinical research plays an important role in medical sciences by determining the safety and efficiency of medications, devices and diagnostic products for human use. Our discovery of the interactions between intracellular signaling pathways as mediated by Ca 2+ and cAMP (Ca 2+ /cAMP signaling interaction) in neurotransmission could help improve cli...

Cardiovascular diseases (CD) are one of the main causes of death in the world, among them is ischemic cardiac disease (ICD). ICD is believed to cause 26 million deaths worldwide by 2030 [1,2]. Among ICD, acute myocardial infarction (AMI) is the most common cause of morbidity and mortality in the world [2,3]. AMI is characterized by a long period, a...

It is now well-established that the signalling pathways mediated by Ca 2+ and cAMP can interact (Ca 2+ /cAMP signalling interaction), thus playing a vital role in cellular processes of mammalians. In the neurology and medicine, it has opened novel opportunities for the development of pharmaceuticals more efficient, and safer, for treating neurodege...

The pharmacotherapy for treating depression is clearly limited. The classical pharmacotherapy that exists nowadays was developed decades ago. Indeed, depression is characterized by reduction of neurotransmitters release in central nervous system, mainly serotonin and catecholamines. Besides, since 70´s several clinical studies have reported that ad...

This discusses how pharmacological modulation of the Ca2+/cAMP signaling interaction could be an important neuroprotective and cardioprotective strategy to protect the dopaminergic neurons from cell death related to Parkinson’s disease (PD) and at the same time to prevent the cardiac collapse in sudden unexpected death in PD.

Several experimental studies performed since 1975, using smooth muscles richly innervated by sympathetic nerves to exclude the autonomic influence of adjusting reflex (rodent vas deferens), showed that L-type voltage-activated Ca 2+ channels (VACC) blockers completely inhibited neurogenic contractions induced by electrical field stimulation (EFS) i...

In 2013, we showed that the paradoxical effects (sympathetic hyperactivity) induced by L-type voltage-activated Ca2+ channels (VACC) blockers, named by us “calcium paradox” phenomenon, were potentiated by drugs which increase cytosolic cAMP concentration ([cAMP]c-enhancers), for example rolipram, IBMX and forskolin, indicating that the sympathetic...

The sympathetic hyperactivity, and tachycardia, are the main adverse effects reported since 70´s by hyperten-sive patients that use L-type Ca 2+ channel blockers (CCBs). Our discovery revealed that the sympathetic hyperactivity was resulting of increase of transmitter release from sympathetic neurons stimulated by CCBs due to its interference on th...

What have we learned from the discovery of the " calcium paradox " due to Ca 2+ /cAMP interaction? Our discovery of the involvement of interaction between the intracellular signalling pathways mediated by Ca 2+ and cAMP (Ca 2+ /cAMP interaction) in the neuronal protection has produced new paths for the understanding of the cellular and molecular me...

It is now well-accepted that the interaction between intracellular signalling pathways mediated by Ca 2+ and cAMP (Ca 2+ /cAMP signalling interaction) plays as a key role in cellular processes of mammalians. In the clinical pathology field, it has opened a new avenue for the drug development more effective, and safer, for the treatment of neurodege...

This editorial focus on the new therapeutic perspectives for Alzheimer's and Parkinson's diseases based on the pharmacological modulation of the Ca2+/cAMP signaling interaction.

It is well recognized that an imbalance of intracellular Ca2+ homeostasis contributes to the pathogenesis of neurodegenerative diseases, such as Alzheimer's (AD). Therefore, regulation of intracellular Ca2+ homeostasis may represent a new target for treatment of this disease. Our recent discovery of the participation of the interaction between intr...

This editorial article gives insights for the inhibition of cancer progression. The pharmacological modulation of Ca2+/cAMP signalling interaction is also cited.

It has been almost 4 years since we revealed the explanation for the enigma of the so-called " calcium paradox ". Interestingly, this discovery initiated decades ago when numerous clinical studies have reported that use of L-type Ca 2+ channel blockers (CCBs) by hypertensive patients decreased arterial pressure, but produced typical symptoms of sym...

Editorial: Without a doubt, we decided to initiate our first editorial article in this journal with the transcription of the " prologue " of our book: From discovering " calcium paradox " to Ca2+/cAMP interaction: Impact in human health and disease...

Our discovery of the involvement of the interaction between intracellular signalling pathways mediated by Ca2+ and cAMP (Ca 2+ /cAMP interaction) in the neurotransmission and neuroprotection has produced new avenues in the understanding of the cellular and molecular mechanisms involved in the pathogenesis of neurological and psychiatric disorders,...

It has been almost 4 years since we revealed the explanation for the enigma of the so-called " calcium paradox ". Our discovery of the involvement of Ca 2+ /cAMP signaling interaction in the regulation of neurotransmitter release, and neuroprotection, was clearly a serendipitous discovery. It has produced new avenues in the understanding of the cel...

Depression is a psychiatric disease resulting mainly by dysfunction of serotoninergic and monoaminergic neurotransmission in central nervous system (CNS). Due to the multifaceted nature of depression and our limited understanding on its etiology, depression is difficult to be treated with currently available pharmaceuticals. Then, new therapeutic s...

In the cardiovascular field, tachycardia and increment of catecholamine plasma levels (sympathetic hyperactivity) have been reported by hypertensive patients that use L-type Ca2+ channel blockers (CCBs) since 70´s. Our discovery of the involvement of interaction between the intracellular signalling pathways mediated by Ca2+ and cAMP (Ca2+/cAMP inte...

Our discovery entitled " calcium paradox " phenomenon due to interaction of intracellular signalling pathways mediated by Ca 2+ and cAMP (Ca2+/cAMP interaction) may provide new avenues for the treatment of neurologi-cal disorders, such as Alzheimer´s disease. This disease is resulting by reduction of acetylcholine release in central nervous system...

Abstract It is well established that an imbalance of neuronal Ca2+ homeostasis contributes to the pathogenesis of neurodegenerative diseases, such as Alzheimer's (AD) and Parkinson's (PD) diseases. Therefore, regulation of neuronal Ca2+ homeostasis may represent a new therapeutic strategy of these diseases. Our recent discovery of the involvement o...

The pharmacological manipulation of interaction of the intracellular signalling pathways mediated by Ca 2+ and cAMP (Ca 2+ /cAMP interaction) may provide new insights for the pharmacotherapy of psychiatric disorders, dramatically impacting clinical pharmacology and translational medicine. Disorders mainly resulting by reduction of serotonin and cat...

Our discovery of the involvement of the interaction between intracellular signalling pathways mediated by Ca2+ and cAMP (Ca2+/cAMP signaling interaction) in the neurotransmission and neuroprotection has produced important advances in the understanding of the pathophysiology and pharmacology of neurological and psychiatric disorders, such as Alzheim...