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

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

Risultato della ricerca: Contributo in rivistaArticolo in rivista

7 Citazioni (Scopus)

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 Ca 2+ measures in striatal brain slices and differentiated SH-SY5Y cells showed that co-application of α-syn and the neurotoxic pesticide rotenone (Rot) induced Ca 2+ 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 Ca 2+ homeostasis in PD and that its inhibition most likely exerts a protective effect in the toxicity induced by α-syn and Rot.
Lingua originaleEnglish
pagine (da-a)N/A-N/A
RivistaCELL DEATH & DISEASE
Volume10
DOI
Stato di pubblicazionePubblicato - 2019

Keywords

  • mitochondrial
  • α-synuclein

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