Afonso Caricati-Neto*, Leandro Bueno Bergantin
Department of Pharmacology, Laboratory of Autonomic and Cardiovascular Pharmacology, Escola Paulista de Medicina, Universidade Federal de São Paulo (UNIFESP), 55 11 5576-4973, Rua Pedro de Toledo, 669 - Vila Clementino, São Paulo - SP, Brazil, Postal Code: 04039-032.
Prof. Dr. Afonso Caricati-Neto
Department of Pharmacology,
Laboratory of Autonomic and Cardiovascular Pharmacology,
Escola Paulista de Medicina, Universidade Federal de São Paulo (UNIFESP), 55 11 5576-4973, Rua Pedro de Toledo, 669 - Vila Clementino, São Paulo - SP, Brazil, Postal Code: 04039-032.
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 of the interaction between intracellular signaling pathways mediated by Ca2+ and cAMP (Ca2+/cAMP signaling interaction) in the neurotransmission and neuroprotection, and its pharmacological modulation, has contributed to the understanding of pathophysiology and pharmacology of neurodegenerative diseases. This discovery emerged from numerous clinical studies performed since 1975 that reported that the use of L-type Ca2+ channel blockers (CCBs) during the antihypertensive therapy decreased arterial pressure, but produced typical symptoms of sympathetic hyperactivity such as tachycardia and increment of catecholamine plasma levels. Despite these adverse effects have been initially attributed to adjust reflex of arterial pressure, during almost four decades this phenomenon remained unclear. In 2013, we discovered that this sympathetic hyperactivity is due to increase of transmitter release from sympathetic neurons and adrenal chromaffin cells caused by the modulatory action of CCBs on the Ca2+/cAMP signaling interaction. Additionally, we discovered that the pharmacological modulation of neural Ca2+/cAMP signaling interaction can reduce neuronal death due to attenuation of cytosolic Ca2+ overload and stimulation of cell survival pathways mediated by cAMP-response element binding protein (CREB). Then, our discovery of the pharmacological modulation of neural Ca2+/cAMP signaling interaction may open a large avenue for the development of a new therapeutic strategy for AD and PD.
Keywords: Ca2+/cAMP signaling interaction; Alzheimer’s disease, Parkinson’s disease, neurological/psychiatric disorders