Review Article Open Access

Perspectives of The Pharmacological Modulation of Ca²⁺/ Camp Signaling Interaction as a New Neuroprotector Therapeutic Strategy for Amyotrophic Lateral Sclerosis (ALS)

Afonso Caricati-Neto and Leandro Bueno Bergantin*

DOI: 10.26717/BJSTR.2017.01.000131

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- Department of Pharmacology, Federal University of São Paulo (UNIFESP), Brazil
*Corresponding author: Leandro Bueno Bergantin, Laboratory of Autonomic and Cardiovascular Pharmacology, Department of Pharmacology, Escola Paulista de Medicina, Universidade Federal de São Paulo (UNIFESP), Phone-55 11 5576-4973, Rua Pedro de Toledo, 669 – Vila Clementino, São Paulo-SP, Brazil

Received: May 31, 2017 Published: June 15, 2017

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Abstract

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 of motor neurons in ALS. It is now recognized that the interaction between intracellular signaling pathways mediated by Ca²⁺ and cAMP (Ca²⁺/cAMP signalling interaction) plays as a key role in several cellular processes of mammalians, including neurotransmission and neuroprotection.

Our previous studies have indicated that the pharmacological modulation of the Ca2+/cAMP signalling interaction by the combined use of the Ca²⁺ channel blockers (CCBs) and drugs that increment of the intracellular concentration of cAMP (cAMP-enhancer compounds) can increase neurotransmission, and stimulate neuroprotective response in neurodegenerative diseases. We have proposed that the pharmacological modulation of Ca²⁺/cAMP signalling interaction could open a new avenue for the drug development more effective and safer for treating neurodegenerative diseases, including ALS. In this review article, we discuss the perspectives of the pharmacological modulation of the Ca²⁺/ cAMP signalling interaction as a new therapeutic strategy for ALS.

Keywords: Ca²⁺/cAMP signaling interaction; Neurodegenerative diseases; Amyotrophic lateral sclerosis (ALS)

Introduction | The pharmacological Modulation of the Ca²⁺/cAMP signalling interaction in neurodegenerative diseases | The pharmacological Modulation of the Ca²⁺/cAMP Signalling Interaction as a new Neuroprotector Therapeutic Strategy for amyotrophic lateral Sclerosis | Conclusion | References | Figures |