Contribution of Sodium-Calcium Exchanger Isoform-3 in Aβ1-42 Induced Cell DeathAuthor(s): Henok Kessete Afewerky, Hao Li, Pei Pang, Tongmei Zhang, Youming Lu
Aβ1-42 is a peptide which can alter intracellular calcium (Ca2+) homeostasis and subsequently cause cell death. The molecular mechanisms underlying Aβ1-42 induced Ca2+ dyshomeostasis and neurodegeneration are not fully elucidated. The third isoform of the sodium-calcium exchanger (NCX) family, NCX3, plays a vital role in adjusting excitable cells Ca2+ homeostasis. In this study, using NCX3 stably transfected baby hamster kidney (BHK) cells, we aim to study the role of NCX3 against Aβ1-42 induced cell death. Our result demonstrates that NCX3 stably transfected cells (BHK-NCX3) are more resistant to Aβ1-42 aggregation compared to their wild types (BHK-WT). The increased cellular loss in BHK-WT was correlated to increased cytoplasmic Ca2+ concentration ([Ca2+]i) induced by Aβ1-42. These results present that NCX3 protects against Aβ1-42 induced cell death and proclaim NCX3 and its downstream molecular pathways as critical components that take part in Aβ1-42 neurotoxicity. Our study substantiates molecular events through which Aβ1-42 can induce neurodegeneration such as Alzheimers disease and marks potential targets to slow down neuropathogenesis.