Endoplasmic Reticulum Stress: Its Role in Disease and Novel Prospects for Therapy

Table 1

Human diseases linked to ER stress.

Disease	Linkage to ER stress	References
Type 2 diabetes	(i) Obesity induces ER stress; (ii) Hyperlipidemia and hyperglycemia induce ER stress; (iii) Free fatty acids (palmitate) induce beta cell apoptosis; (iv) Deletion of CHOP improves beta cell function and survival	[31, 34, 98, 119, 127, 142, 288]
Atherosclerosis	(i) Oxidized lipids induce ER stress; (ii) Hyperhomocysteinemia induces ER stress; (iii) Cholesterol loading induces ER stress-mediated cell death; (iv) Reduced plaque necrosis in mice lacking CHOP	[289–295]
Nonalcoholic fatty liver disease	(i) Forced GRP78 expression reduces hepatic steatosis in mice; (ii) ER stress activates cholesterol and triglyceride biosynthesis; (iii) Hyperlipidemia and hyperglycemia induce ER stress	[296–299]
Alcoholic liver disease	(i) Alcohol induces ER stress	[32, 300, 301]
Heart disease	(i) ER stress contributes to cardiac myocyte apoptosis; (ii) Activation of ER stress in infarcted mouse heart; (iii) GRP78 and GRP94 protect against ischemic injury	[302–308]
HBV and HCV infection	(i) HBV induces GRP78 and GRP94; (ii) HCV suppresses IRE1/XBP1 pathway	[309–312]
Alzheimer’s disease	(i) Mutant presenilin 1 induces ER stress; (ii) Mutant presenilin 1 sensitizes to ER stress-induced apoptosis; (iii) AD brains show ER stress features	[313–318]
Parkinson’s disease	(i) Parkin expression impacts ER stress; (ii) ATF4 leads to increase in parkin expression	[317–321]
Huntington disease	(i) Polyglutamine induces ER stress; (ii) ER stress markers are present in postmortem HD brain	[322–327]
Amyotrophic lateral sclerosis	(i) Mutant SOD1 activates ER stress; (ii) Mutant SOD1 interferes with ERAD; (iii) ER stress markers detected in spinal cord of ALS patients	[318, 328–330]
Prion disease	(i) ER stress markers detected in brains affected with prions; (ii) ER chaperones are involved in regulation of misfolded prion protein	[331–334]
Cancer	(i) Tumor-specific microenvironment activates ER stress; (ii) Cancer cells display chronic display of ER stress markers; (iii) Knockdown of GRP78 or of CHOP affects chemosensitivity	[83, 97, 151, 222, 335–337]