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Evaluation of control of apoE expression by corticosterone and T4 and cytokine IL-6

Grant number: 18/10381-5
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): August 01, 2018
Effective date (End): December 31, 2019
Field of knowledge:Biological Sciences - Biochemistry - Molecular Biology
Principal researcher:Kil Sun Lee
Grantee:Gabriela Cruz Pereira
Home Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

Alzheimer's disease (AD) is a neurodegenerative disease triggered by several factors, including the accumulation of ²-amyloid peptides (pA²), which leads to loss of synapses and neurons. These peptides are generated from the proteolytic cleavage of the amyloid precursor protein (APP) and can modulate a neuronal activity. Subsequently, these peptides can be degraded in the brain or drained to the peripheral system through the blood-brain barrier (BBB). In both cases, lipoprotein receptors play an important role in endocytosis or transcytosis. Apolipoprotein E (apoE) is a protein that binds to lipoprotein receptors and participates in the lipid metabolism of various tissues. There are controversial data about the apoE role in pA² degradation in the brain. ApoE may bind to pA² and facilitate endocytosis of pA² via lipoprotein receptors or it may compete with pA² for binding to these receptors. Therefore, additional studies are required to better understand the role of apoE in the metabolism of pA². It is known that the expression of ApoE is regulated by factors such as glucocorticoid (GR) receptors, cytokines and thyroid hormone (TR²). During sleep deprivation, levels of these hormones and cytokines are altered, suggesting that sleep deprivation may alter the apoE levels. Moreover, sleep deprivation has been pointed out as one of the risk factors for AD. Thus, the main objective of this study is to investigate the effects of hormonal profile established during sleep deprivation on the apoE expreesion using in vitro culture of neurons and glia. This study can help to elucidate the relationship between AD, sleep deprivation and the role of apoE.