Question

2. How is the unfolded protein response involved in prion neurotoxicity?

2. How is the unfolded protein response involved in prion neurotoxicity?

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Answer #1

Answer -Prions is an abnormal form of a normally harmless protein found in the brain. Which is responsible for a variety of fatal neurodegenerative diseases of animals, including humans, called transmissible spongiform encephalopathies.

We analyzed activation of the unfolded protein response (UPR) during rising levels of prion protein accumulation during the course of disease as protein priorn (PrP )is synthesized in the endoplasmic reticulum ( ER).We found that there was a progressive increase in PERK-P and eIF2α-P as the disease progressed.  GADD34 levels did not change, despite the rising eIF2α-P levels, suggesting that there was insufficient GADD34 to dephosphorylate the increased amounts of eIF2α-P. This shows that the PERK/eIF2α arm of the UPR is activated in prion disease, inhibiting protein translation and leading to a reduction in the levels of synaptic proteins.

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