Discovery of the Aβ receptor that controls the voltage-gated sodium channel activity: unraveling mechanisms underlying neuronal hyperexcitability.

Alzheimer's disease (AD) is characterized by a gradual decline in memory and cognitive abilities, often accompanied by personality changes and impairments in motor functions. Increased neuronal activity in AD patients is associated with the symptoms of the disease, suggesting a link between hyperactivity and cognitive decline. In particular, amyloid beta peptides (Aβs), which are implicated in AD, have been found to enhance voltage-gated sodium channels (VGSCs), crucial for generating nerve impulses. However, the exact mechanisms underlying this interaction remain poorly understood. Therefore, it is crucial to identify the membrane receptor that binds to Aβ and regulates VGSC activity. In this report, we employed the patch-clamp method to monitor alterations in VGSCs induced by Aβ. Through gene silencing and antibody treatment, we determined that the receptor responsible for regulating VGSCs corresponds to the type I taste receptor (T1R2/T1R3). Our discovery not only advances the understanding of Aβ's physiological role but also opens avenues for developing molecules that can inhibit or alter Aβ binding, potentially regulating neuronal hyperactivity in AD.NEW & NOTEWORTHY Alzheimer's disease (AD) is marked by memory loss and cognitive decline, with neuronal hyperactivity linked to amyloid beta peptides (Aβs) that enhance sodium channels. Using patch-clamp techniques, we determined that the receptor for Aβ corresponds to the type I taste receptor (T1R2/T1R3). This discovery reveals Aβ's physiological roles and offers a new molecular target for developing therapies to inhibit or modify Aβ binding, potentially regulating neurohyperactivity in AD.