title: Antagonizing amyloid-β/calcium-sensing receptor signaling in human astrocytes and neurons: a key to halt Alzheimer's disease progression?
abstract: Astrocytes' roles in late-onset Alzheimer's disease (LOAD) promotion are important, since they survive soluble or fibrillar amyloid-β peptides (Aβs) neurotoxic effects, undergo alterations of intracellular and intercellular Ca(2+) signaling and gliotransmitters release via the Aβ/α7-nAChR (α7-nicotinic acetylcholine receptor) signaling, and overproduce/oversecrete newly synthesized Aβ42 oligomers, NO, and VEGF-A via the Aβ/CaSR (calcium-sensing receptor) signaling. Recently, it was suggested that the NMDAR (N-methyl-D-aspartate receptor) inhibitor nitromemantine would block the synapse-destroying effects of Aβ/α7-nAChR signaling. Yet, this and the progressive extracellular accrual and spreading of Aβ42 oligomers would be stopped well upstream by NPS 2143, an allosteric CaSR antagonist (calcilytic).
authors.affiliation: Histology & Embryology Section, Department of Life & Reproduction Sciences, University of Verona Medical School, Verona, Venetia, I-37134, Italy.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Dal Prà
authors.affiliation: Histology & Embryology Section, Department of Life & Reproduction Sciences, University of Verona Medical School, Verona, Venetia, I-37134, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Chiarini
authors.affiliation: Histology & Embryology Section, Department of Life & Reproduction Sciences, University of Verona Medical School, Verona, Venetia, I-37134, Italy.
authors.forename: Ubaldo
authors.initials: U
authors.lastname: Armato
keywords: Alzheimer's disease; Ca2+; NPS 2143; amyloid-β; astrocytes; calcilytic; calcium-sensing receptor; nitromemantine; α7-nicotinic acetylcholine receptor