A timeline of Ca2+/cAMP signalling: From basic research to potential therapeutics for dementia.

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 exercise, a self-control in caloric ingestion, and participating in intellectually challenging events. These lifestyle factors may alleviate the excess of Ca2+ resulted from a Ca2+ dyshomeostasis. Curiously, epidemiological, and clinical studies have also reported a clinical relationship among hypertension, diabetes and other inflammatory processes, and a higher risk for a decline of cognition. 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 From 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 the role of Ca2+ channel blockers for restoring Ca2+ signalling disruption due to COVID-19. Finally, this article also presents a timeline of the major events in Ca2+/cAMP signaling.