Staufen 1 amplifies proapoptotic activation of the unfolded protein response.

Staufen-1 (STAU1) is a protein RNA-binding becomes very overabundant in various models of neurodegenerative diseases, including those who carry mutations in presenilin1 (PSEN1), microtubule-associated protein tau (MAPT), huntingtin (HTT), TAR DNA-binding protein -43 gene (TARDBP), or C9orf72.

We previously reported that the increase in STAU1 determine defects and knockdown autophagy is protective in models of several neurodegenerative diseases. Additional functional consequences STAU1 overwhelming, however, has not been investigated. We studied the role of chronic activation STAU1 in the folded protein response (UPR), a common feature of neurodegenerative diseases and are often directly related to the death of neurons.

Here we report that STAU1 is a novel modulator of the UPR, and is required for apoptosis induced by activation of a perk-CHOP. STAU1 levels increase in response to some of the endoplasmic reticulum (ER) stress, and expression of exogenous STAU1 enough to cause apoptosis through pathways of UPR perk-CHOP. cortical neurons and skin fibroblasts derived from Stau1 – / – mice showed a decrease in the UPR and apoptosis when challenged with thapsigargin.

In fibroblasts from individuals with SCA2 or with ALS causes and C9ORF72 TDP-43 mutations, we found extremely elevated levels of STAU1 and CHOP in basal conditions, and STAU1 knockdown CHOP levels returned to normal. Taken together, these results suggest that STAU1 overabundance reduce cellular resistance to ER stress and apoptosis deposition.

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