Abstract
Excitotoxic mechanisms of neuronal death can occur in the presence of excess glutamate. Hence, means to remove or convert extra-neuronal glutamate exist in brain. However, in Alzheimer’s disease (AD) brain, the glutamate transporter and glutamine synthestase function with considerably reduced activity. Consistent with the observed oxidative stress in AD brain and the oxidative stress induced by amyloid β-peptide (Aβ), both the glutamate transporter (EAAT2) and glutamine synthetase are oxidatively modified in AD brain. Moreover, Aβ causes EAAT2 and glutamine synthetase to be oxidized, consistent with the notion that excess Aβ in AD brain contributes to the oxidative stress observed. This chapter reviews studies that support the notion that the dysfunctional glutamatergic system in AD brain results from oxidative modifications of key components of this system, and that Aβ plays a role in this oxidative modification. Consequent excitotoxicity could be one means to account for neuronal and synapse loss in AD brain.
Published Version
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