New perspectives for selective NCX activators in neurodegenerative diseases

Lucio Annunziato; Agnese Secondo; Giuseppe Pignataro; Antonella Scorziello; Pasquale Molinaro

doi:10.1016/j.ceca.2020.102170

New perspectives for selective NCX activators in neurodegenerative diseases

Cell Calcium. 2020 May:87:102170. doi: 10.1016/j.ceca.2020.102170. Epub 2020 Feb 7.

Authors

Lucio Annunziato¹, Agnese Secondo², Giuseppe Pignataro³, Antonella Scorziello⁴, Pasquale Molinaro⁵

Affiliations

¹ IRCSS SDN, Via Gianturco, 80131, Naples, Italy. Electronic address: lannunzi@unina.it.
² Division of Pharmacology, Department of Neuroscience, Reproductive and Odontostomatologic Sciences, School of Medicine, "Federico II" University of Naples, 80131 Naples, Italy. Electronic address: secondo@unina.it.
³ Division of Pharmacology, Department of Neuroscience, Reproductive and Odontostomatologic Sciences, School of Medicine, "Federico II" University of Naples, 80131 Naples, Italy. Electronic address: gpignata@unina.it.
⁴ Division of Pharmacology, Department of Neuroscience, Reproductive and Odontostomatologic Sciences, School of Medicine, "Federico II" University of Naples, 80131 Naples, Italy. Electronic address: scorziel@unina.it.
⁵ Division of Pharmacology, Department of Neuroscience, Reproductive and Odontostomatologic Sciences, School of Medicine, "Federico II" University of Naples, 80131 Naples, Italy. Electronic address: pmolinar@unina.it.

PMID: 32106022
DOI: 10.1016/j.ceca.2020.102170

Abstract

The Na⁺/Ca²⁺ exchanger plays a relevant role in several neurological disorders, thus the pharmacological modulation of its isoforms might represent a promising strategy to ameliorate the course of some neurological pathologies including stroke, neonatal hypoxia, multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), Alzheimer Disease (AD), and spinal muscular atrophy (SMA). This review will summarize heterocyclic, peptidergic, genetic and epigenetic compounds activating or inhibiting the expression/activity of each NCX isoform. In addition, we will focus our attention on the development of new strategies aimed to ameliorate the pathophysiological conditions in which NCX isoform changes are found.

Keywords: Drug development; NCX1; NCX2; NCX3; Neurodegenerative diseases; Stroke.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Animals
Cell-Penetrating Peptides / metabolism
Epigenesis, Genetic
Humans
Neurodegenerative Diseases / genetics
Neurodegenerative Diseases / metabolism*
Neurodegenerative Diseases / physiopathology
Protein Isoforms / metabolism
Sodium-Calcium Exchanger / metabolism*

Substances

Cell-Penetrating Peptides
Protein Isoforms
Sodium-Calcium Exchanger