000095678 001__ 95678 000095678 005__ 20210902121627.0 000095678 0247_ $$2doi$$a10.1016/j.nbd.2020.104809 000095678 0248_ $$2sideral$$a117177 000095678 037__ $$aART-2020-117177 000095678 041__ $$aeng 000095678 100__ $$0(orcid)0000-0002-1557-7545$$aMartínez-Martínez, Ana B.$$uUniversidad de Zaragoza 000095678 245__ $$aBeyond the CNS: The many peripheral roles of APOE 000095678 260__ $$c2020 000095678 5060_ $$aAccess copy available to the general public$$fUnrestricted 000095678 5203_ $$aApolipoprotein 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 (e2, e3, and e4). 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. 000095678 536__ $$9info:eu-repo/grantAgreement/ES/DGA/B03-17R$$9info:eu-repo/grantAgreement/ES/ISCIII/FIS/PI17-02268 000095678 540__ $$9info:eu-repo/semantics/openAccess$$aby-nc-nd$$uhttp://creativecommons.org/licenses/by-nc-nd/3.0/es/ 000095678 590__ $$a5.996$$b2020 000095678 591__ $$aNEUROSCIENCES$$b54 / 273 = 0.198$$c2020$$dQ1$$eT1 000095678 592__ $$a2.205$$b2020 000095678 593__ $$aNeurology$$c2020$$dQ1 000095678 655_4 $$ainfo:eu-repo/semantics/review$$vinfo:eu-repo/semantics/publishedVersion 000095678 700__ $$aTorres-Perez, Elena 000095678 700__ $$aDevanney, Nicholas 000095678 700__ $$aDel Moral, Raquel 000095678 700__ $$aJohnson, Lance A. 000095678 700__ $$0(orcid)0000-0002-8982-3737$$aArbones-Mainar, José M. 000095678 7102_ $$11006$$2255$$aUniversidad de Zaragoza$$bDpto. Fisiatría y Enfermería$$cÁrea Enfermería 000095678 773__ $$g138 (2020), 104809 1-11$$pNeurobiol. dis.$$tNeurobiology of disease$$x0969-9961 000095678 8564_ $$s909763$$uhttps://zaguan.unizar.es/record/95678/files/texto_completo.pdf$$yVersión publicada 000095678 8564_ $$s68731$$uhttps://zaguan.unizar.es/record/95678/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada 000095678 909CO $$ooai:zaguan.unizar.es:95678$$particulos$$pdriver 000095678 951__ $$a2021-09-02-08:51:05 000095678 980__ $$aARTICLE