Gateways for Glutamate Neuroprotection in Parkinson’s Disease (PD): Essential Role of EAAT3 and NCX1 Revealed in an In Vitro Model of PD

Autor: Alessandra Preziuso, Silvia Piccirillo, Salvatore Amoroso, Pasqualina Castaldo, Simona Magi, Vincenzo Lariccia
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Zdroj: Cells
Volume 9
Issue 9
Cells, Vol 9, Iss 2037, p 2037 (2020)
ISSN: 2073-4409
DOI: 10.3390/cells9092037
Popis: Increasing evidence suggests that metabolic alterations may be etiologically linked to neurodegenerative disorders such as Parkinson&rsquo
s disease (PD) and in particular empathizes the possibility of targeting mitochondrial dysfunctions to improve PD progression. Under different pathological conditions (i.e., cardiac and neuronal ischemia/reperfusion injury), we showed that supplementation of energetic substrates like glutamate exerts a protective role by preserving mitochondrial functions and enhancing ATP synthesis through a mechanism involving the Na+-dependent excitatory amino acid transporters (EAATs) and the Na+/Ca2+ exchanger (NCX). In this study, we investigated whether a similar approach aimed at promoting glutamate metabolism would be also beneficial against cell damage in an in vitro PD-like model. In retinoic acid (RA)-differentiated SH-SY5Y cells challenged with &alpha
synuclein (&alpha
syn) plus rotenone (Rot), glutamate significantly improved cell viability by increasing ATP levels, reducing oxidative damage and cytosolic and mitochondrial Ca2+ overload. Glutamate benefits were strikingly lost when either EAAT3 or NCX1 expression was knocked down by RNA silencing. Overall, our results open the possibility of targeting EAAT3/NCX1 functions to limit PD pathology by simultaneously favoring glutamate uptake and metabolic use in dopaminergic neurons.
Databáze: OpenAIRE
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