The Interactions Between Alzheimer’s Disease and Major Depression: Role of Ca²⁺ Channel Blockers and Ca²⁺/cAMP Signalling

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: CaCa²⁺ 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.