A Neuronal GPCR Modifies Neuropeptide Signaling to Suppress Proteostasis in distal tissues

However, with aging the competence of the PN declines and aggregated proteins accrue within cells. This process can underlie the development of neurodegenerative disorders, such as Alzheimer’s and Huntington’s diseases.

Although the activities of the PN occur within the cell, this network is regulated across the organism by inter-tissue communication, which is partially governed by neurons. We discovered previously, that reducing the expression of gtr-1, which encodes a neuronal GPCR, protects worms from the toxicity of the Alzheimer’s-causing, Aβ peptide. Here we investigated the mechanism that is acted upon the knockdown of gtr-1 and found that gtr-1 RNAi treatment modulates the expression of neuropeptide-coding genes, differentially modifies the aggregation of proteotoxic proteins, and enhances protein degradation.