Exploring the Role of NCX1 and NCX3 in an In Vitro Model of Metabolism Impairment: Potential Neuroprotective Targets for Alzheimer’s Disease

Alzheimer’s disease (AD) is a widespread neurodegenerative disorder, affecting large number of elderly individuals worldwide. Mitochondrial dysfunction, metabolic alterations, and oxidative stress are regarded as cooperating drivers the progression AD. In particular, impairment amplifies production reactive oxygen species (ROS), resulting in detrimental alterations to intracellular Ca2+ regulatory processes. The Na+/Ca2+ exchanger (NCX) proteins key pathophysiological determinants Na+ homeostasis, operating at both plasma membrane mitochondria levels. Our study aimed explore role NCX1 NCX3 retinoic acid (RA) differentiated SH-SY5Y cells treated with glyceraldehyde (GA), induce default glucose metabolism that typically precedes Aβ deposition or Tau protein phosphorylation By using an RNA interference-mediated approach silence either expression, we found that, GA-treated cells, knocking-down ameliorated cell viability, increased ATP production, reduced damage. Remarkably, silencing also prevented enhancement pTau levels normalized GA-induced decrease NCX reverse-mode activity. contrast, was totally ineffective preventing cytotoxicity except for increase synthesis. These findings indicate may differently influence evolution AD pathology fostered by thus providing potential target