1.
Beyond the CNS: The many peripheral roles of APOE.
Martínez-Martínez, AB, Torres-Perez, E, Devanney, N, Del Moral, R, Johnson, LA, Arbones-Mainar, JM
Neurobiology of disease. 2020;:104809
Abstract
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 demonstrated roles 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.
2.
Apolipoprotein E and the risk of breast cancer in African-American and non-Hispanic white women. A review.
Moore, RJ, Chamberlain, RM, Khuri, FR
Oncology. 2004;(2):79-93
Abstract
The apolipoprotein genetic polymorphism (APO E) is part of a broader paradigm, highlighting the role of gene-environment interactions as risk factors for human diseases such as cardiovascular disease, Alzheimer's disease, dementia, atherosclerosis, multiple sclerosis, peripheral artery disease, diabetes, stroke, and most recently, cancer. APO E, a normal constituent of very-low-density lipoproteins and high-density lipoproteins, is involved in many functions, including lipid metabolism, cholesterol transport, tissue repair, immune response and regulation, as well as cell growth and differentiation. The location, frequency and functional effects of this gene have been reviewed elsewhere in terms of cardiovascular disease, Alzheimer's disease, neuromuscular disease, multiple sclerosis, stroke and diabetes. However, while the majority of studies have examined the significance of APO E as a molecular marker for a variety of diseases in multiethnic populations, few evaluate its role as a putative marker of cancer susceptibility. Fewer explore the importance of APO E on the risk of breast cancer, although some report an association. None have been designed to study its relevance as a marker of breast cancer risk in multiethnic populations. The purpose of this review was to evaluate the association between APO E and the risk for breast cancer in non-Hispanic white and African-American women.