TY - JOUR
T1 - Beyond the CNS
T2 - The many peripheral roles of APOE
AU - Martínez-Martínez, Ana B.
AU - Torres-Perez, Elena
AU - Devanney, Nicholas
AU - Del Moral, Raquel
AU - Johnson, Lance A.
AU - Arbones-Mainar, Jose M.
N1 - Publisher Copyright:
© 2020 The Authors
PY - 2020/5
Y1 - 2020/5
N2 - Apolipoprotein E (APOE) is a multifunctional protein synthesized and secreted by multiple mammalian tissues. Although hepatocytes contribute about 75% of the peripheral pool, APOE can also be expressed in adipose tissue, the kidney, and the adrenal glands, among other tissues. High levels of APOE production also occur in the brain, where it is primarily synthesized by glia, and peripheral and brain APOE pools are thought to be distinct. In humans, APOE is polymorphic, with three major alleles (ε2, ε3, and ε4). These allelic forms dramatically alter APOE structure and function. Historically, the vast majority of research on APOE has centered on the important role it plays in modulating risk for cardiovascular disease and Alzheimer's disease. However, the established effects of this pleiotropic protein extend well beyond these two critical health challenges, with a demonstrated roles for APOE across a wide spectrum of biological conditions, including adipose tissue function and obesity, metabolic syndrome and diabetes, fertility and longevity, and immune function. While the spectrum of biological systems in which APOE plays a role seems implausibly wide at first glance, there are some potential unifying mechanisms that could tie these seemingly disparate disorders together. In the current review, we aim to concisely summarize a wide breadth of APOE-associated pathologies and to analyze the influence of APOE in the development of several distinct disorders in order to provide insight into potential shared mechanisms implied in these various pathophysiological processes.
AB - Apolipoprotein E (APOE) is a multifunctional protein synthesized and secreted by multiple mammalian tissues. Although hepatocytes contribute about 75% of the peripheral pool, APOE can also be expressed in adipose tissue, the kidney, and the adrenal glands, among other tissues. High levels of APOE production also occur in the brain, where it is primarily synthesized by glia, and peripheral and brain APOE pools are thought to be distinct. In humans, APOE is polymorphic, with three major alleles (ε2, ε3, and ε4). These allelic forms dramatically alter APOE structure and function. Historically, the vast majority of research on APOE has centered on the important role it plays in modulating risk for cardiovascular disease and Alzheimer's disease. However, the established effects of this pleiotropic protein extend well beyond these two critical health challenges, with a demonstrated roles for APOE across a wide spectrum of biological conditions, including adipose tissue function and obesity, metabolic syndrome and diabetes, fertility and longevity, and immune function. While the spectrum of biological systems in which APOE plays a role seems implausibly wide at first glance, there are some potential unifying mechanisms that could tie these seemingly disparate disorders together. In the current review, we aim to concisely summarize a wide breadth of APOE-associated pathologies and to analyze the influence of APOE in the development of several distinct disorders in order to provide insight into potential shared mechanisms implied in these various pathophysiological processes.
KW - Diabetes
KW - Fertility
KW - Mechanisms
KW - Obesity
KW - Review
UR - http://www.scopus.com/inward/record.url?scp=85079840909&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85079840909&partnerID=8YFLogxK
U2 - 10.1016/j.nbd.2020.104809
DO - 10.1016/j.nbd.2020.104809
M3 - Review article
C2 - 32087284
AN - SCOPUS:85079840909
SN - 0969-9961
VL - 138
JO - Neurobiology of Disease
JF - Neurobiology of Disease
M1 - 104809
ER -