Journal de la maladie d'Alzheimer et du parkinsonisme

Abstrait

Roles of Sodium-Calcium Exchanger Isoform-3 toward Calcium Ion Regulation in Alzheimers Disease

Henok KA, Tongmei Zhang, Hao Li and Youming Lu

Alzheimer’s disease (AD) is a late-onset progressive neurodegenerative disorder that leads to cognitive, memory and behavioural impairments. Substantial evidence indicates that disrupted neuronal calcium homeostasis is an early event in AD that could mediate synaptic dysfunction and neuronal toxicity. Sodium calcium exchangers (NCXs) play important roles in regulating intracellular calcium, and accumulated data suggests that reduced NCX function, following aberrant proteolytic cleavage of these exchangers, may contribute to neurodegeneration. This review, characterizes the expression and activity of NCX as a prominent feature of AD brain, identifies the molecular mechanisms underlying the effects of NCX isoforms, and pinpoints the molecular determinants responsible for the effects of NCX. Our findings suggest that calpain mediates cleavage of NCX3 in AD brain and therefore that reduced NCX3 activity contributes to the sustained increases in intraneuronal calcium concentrations that are associated with caspase-12 activation and neuronal death in AD.