Figure 4.

Underlying cellular mechanisms of Alzheimer’s disease (AD). The upstream key hallmarks of AD range from ionic dysfunction to the impairment of several cellular processes, including Ca²⁺-signaling dysregulation, abnormal Aβ production and aggregation and neuroinflammation. The crosstalk between the mentioned factors, leads to the pathological phenotype, involving mitochondrial dysfunction, excitotoxicity, and extrasynaptic NMDA receptor (eNMDAR) activation. As the symptomatic circle closes, the dysfunction of one leads to further activation of the others, altogether contributing to neurodegeneration and cognitive deficits, characteristics of the disease.