Selective inhibition of mitochondrial sodium-calcium exchanger protects striatal neurons from α-synuclein plus rotenone induced toxicity

Guendalina Bastioli, Silvia Piccirillo, Pasqualina Castaldo, Simona Magi, Alessandro Tozzi, Salvatore Amoroso, Paolo Calabresi

Research output: Contribution to journalArticle

Abstract

Progressive accumulation of α-synuclein (α-syn) and exposure to environmental toxins are risk factors that may both concur to Parkinson's disease (PD) pathogenesis. Electrophysiological recordings of field postsynaptic potentials (fEPSPs) and Ca2+ measures in striatal brain slices and differentiated SH-SY5Y cells showed that co-application of α-syn and the neurotoxic pesticide rotenone (Rot) induced Ca2+ dysregulation and alteration of both synaptic transmission and cell function. Interestingly, the presence of the mitochondrial NCX inhibitor CGP-37157 prevented these alterations. The specific involvement of the mitochondrial NCX was confirmed by the inability of the plasma membrane inhibitor SN-6 to counteract such phenomenon. Of note, using a siRNA approach, we found that NCX1 was the isoform specifically involved. These findings suggested that NCX1, operating on the mitochondrial membrane, may have a critical role in the maintenance of ionic Ca2+ homeostasis in PD and that its inhibition most likely exerts a protective effect in the toxicity induced by α-syn and Rot.

Original languageEnglish
Pages (from-to)80
JournalCell Death and Disease
Volume10
Issue number2
DOIs
Publication statusE-pub ahead of print - 2018

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Synucleins
Sodium-Calcium Exchanger
Corpus Striatum
Rotenone
Parkinson Disease
Neurons
Synaptic Potentials
Environmental Exposure
Mitochondrial Membranes
Pesticides
Synaptic Transmission
Small Interfering RNA
Protein Isoforms
Homeostasis
Maintenance
Cell Membrane
Brain

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Selective inhibition of mitochondrial sodium-calcium exchanger protects striatal neurons from α-synuclein plus rotenone induced toxicity. / Bastioli, Guendalina; Piccirillo, Silvia; Castaldo, Pasqualina; Magi, Simona; Tozzi, Alessandro; Amoroso, Salvatore; Calabresi, Paolo.

In: Cell Death and Disease, Vol. 10, No. 2, 2018, p. 80.

Research output: Contribution to journalArticle

Bastioli, Guendalina ; Piccirillo, Silvia ; Castaldo, Pasqualina ; Magi, Simona ; Tozzi, Alessandro ; Amoroso, Salvatore ; Calabresi, Paolo. / Selective inhibition of mitochondrial sodium-calcium exchanger protects striatal neurons from α-synuclein plus rotenone induced toxicity. In: Cell Death and Disease. 2018 ; Vol. 10, No. 2. pp. 80.
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AU - Calabresi, Paolo

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