Biomedical Engineering Reference
In-Depth Information
Chapter 3
Consequences of Stress in the Secretary Pathway: The ER
Stress Response and Its Role in the Metabolic Syndrome
Martin Schröder and Louise Sutcliffe
Abstract
The unfolded protein response (UPR) was originally identified as a signaling network coordinating
adaptive and apoptotic responses to accumulation of unfolded proteins in the endoplasmic reticulum
(ER). More recent work has shown that UPR signaling can be triggered by a multitude of cellular events
and that the UPR plays a critical role in the prevention, and also the progression, of a wide variety of
diseases. Much attention has been paid to the role of the UPR in neurodegenerative diseases in the past.
More recently, important roles for the UPR in diseases associated with the metabolic syndrome have been
discovered. Here we review the role of the UPR in these diseases, including type 2 diabetes, atheroscle-
rosis, fatty liver disease, and ischemia.
Key words:
Apoptosis, Conformational disease, Diabetes, Endoplasmic reticulum, Inflammation,
Neurodegenerative disease, Unfolded protein response
1. Introduction
The mammalian endoplasmic reticulum (ER) is the site for the
synthesis, folding, posttranslational modification, and quality
control of most secretory and transmembrane proteins, an intra-
cellular Ca
2+
store involved in Ca
2+
signaling, the site for synthesis
of phospholipids and other lipids such as cholesterol, and the site
for detoxification of xenobiotic substances. Recently, a role for
the ER in cellular signaling leading to apoptosis, inflammation,
and activation of immune responses has been identified.
Perturbation of any of these functions causes ER stress which is
characterized by an accumulation of unfolded proteins in the ER
(
1
). The different functions of the ER are tightly interconnected.
Perturbation of one function affects another (Fig.
1
). In obese
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