Read the summary and the most important questions on The unfolded protein response is activated in Alzheimer’s disease

• 1 Introduction

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• How can AD be characterized at the protein level?

  It is a disease characterized by the accumulation of misfolded proteins (b amyloid and p-tau)

• How is the unfolded protein response triggered?

  By the sensing of unfolded proteins in the ER, through binding of BiP to the misfolded protein.

• To which structures is BiP bound under normal physiological circumstances?

  • PERK
  • ATF-6
  • IRE-1

• What happens to the to BiP bound structures when BiP binds a misfolded protein?

  BiP is released from PERK, ATF-6 and IRE-1

• WHat are the consequences of the unfolded protein response in the short term?

  • Reduction of translation (downregulation of eIF2a)
    
  • Increased protein degradation
    
  • Increased production of BiP  
    

• What may be the fate of cells under prolonged ER stress?

  Cell apoptosis

• What makes the UPR relevant to AD?

  In AD the current hypothesis is that both amyloid beta and p-tau (which are intracellular and extracellular misfolded proteins) are at the core of pathogenesis. deficient UPR may play a big role in the onset of AD.

• How was the UPR studied?

  By BiP and PERK as markers for UPR activation.

• 2 Material and Methods

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• What kind of species were investigated?

  Elderly humans with AD and elderly humans without AD AND dementia

• 3 Results

• 3.1 Expression levels of BiP/GRP78 are increased in AD temporal cortex and hippocampus

• What might be a pre-eliminary conclusion based on the results for BiP?

  BiP expression is increased in higher stages of AD, this may indicate a relationship between BiP expression and AD progression.