Constitutive XBP-1s-mediated activation of the endoplasmic reticulum unfolded protein response protects against pathological tau.

ABSTRACT: To endure over the organismal lifespan, neurons utilize multiple strategies to achieve protein homeostasis (proteostasis). Some homeostatic mechanisms act in a subcellular compartment-specific manner, but others exhibit trans-compartmental mechanisms of proteostasis. To identify pathways protecting neurons from pathological tau protein, we employed a transgenic Caenorhabditis elegans model of human tauopathy exhibiting proteostatic disruption. We show normal functioning of the endoplasmic reticulum unfolded protein response (UPR^ER) promotes clearance of pathological tau, and loss of the three UPR^ER branches differentially affects tauopathy phenotypes. Loss of function of xbp-1 and atf-6 genes, the two main UPR^ER transcription factors, exacerbates tau toxici

SUBMITTER: Waldherr SM 

PROVIDER: S-EPMC6768869 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature