Table of Contents
How is the unfolded protein response activated?
The unfolded protein response (UPR) is a cellular stress response related to the endoplasmic reticulum (ER) stress. The UPR is activated in response to an accumulation of unfolded or misfolded proteins in the lumen of the endoplasmic reticulum.
What is the relationship between proteins and Alzheimer’s disease?
It is formed from the breakdown of a larger protein, called amyloid precursor protein. One form, beta-amyloid 42, is thought to be especially toxic. In the Alzheimer’s brain, abnormal levels of this naturally occurring protein clump together to form plaques that collect between neurons and disrupt cell function.
What proteins are affected by Alzheimer’s?
Alzheimer’s disease is thought to be caused by the abnormal build-up of proteins in and around brain cells. One of the proteins involved is called amyloid, deposits of which form plaques around brain cells. The other protein is called tau, deposits of which form tangles within brain cells.
How does protein misfolding causes Alzheimer’s?
Alzheimer’s disease (AD) has been identified as a proteopathy: a protein misfolding disease due to the accumulation of abnormally folded amyloid beta (Aβ) protein in the brain.
How does Tunicamycin induce stress?
Tunicamycin (Tun), a naturally occurring antibiotic, induces ER stress in cells by inhibiting the first step in the biosynthesis of N-linked glycans in the proteins resulting many misfolded proteins [16].
Is PERK a transcription factor?
Specifically, whereas ATF4 controlled transcription and was essential for autophagosome formation, PERK acted in a transcription-independent manner and was required at a post-sequestration step in the autophagic pathway.
Are there any treatments for the unfolded protein response?
Targeting the unfolded protein response, and particularly PERK-branch mediated translational failure is thus an increasingly compelling strategy for new treatments for dementia and neurodegenerative disease. Introduction
How does overactivation of the unfolded protein response?
Rather, overactivation of the protein kinase RNA-like ER kinase (PERK, encoded by EIF2AK3) branch of the unfolded protein response directly contributes to disease pathogenesis through the critical reduction in neuronal protein synthesis rates, essential for learning and memory and for neuronal survival.
What are the abbreviations for the unfolded protein response?
Abbreviations ALS amyotrophic lateral sclerosis eIF2 eukaryotic initiation factor PERK protein kinase RNA-like ER kinase UPR unfolded protein response
What are the diseases caused by protein misfolding?
Known collectively as the protein misfolding disorders, they include Alzheimer’s and Parkinson’s diseases, frontotemporal dementia and tauopathies, amyotrophic lateral sclerosis (ALS) and the rare prion diseases.