Evaluation of sleep deprivation effects on function and metabolism of amyloid-beta peptides

• Grant number: 17/10404-2
• Support Opportunities: Scholarships in Brazil - Doctorate
• Effective date (Start): September 01, 2017
• Effective date (End): December 31, 2021
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Kil Sun Lee
• Grantee: Márcio Henrique Mello da Luz
• Host 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 that exhibits important hallmarks as a progressive cognitive decline and the commitment of elderly people. This disease has a significant impact on the mortality rate and the global economy. Despite the efforts made by research groups around the world, the cure for AD has not yet been discovered and the scarce treatment alternatives are only aimed in delaying its progression. It is known that the main molecular characteristics presented by AD patients are the presence of both neurofibrillary tangles composed by tau protein and senile plaques formed by aggregates of amyloid-beta peptide (pAbeta). Another observation in these patients is a higher prevalence of epsilon-4 allele that codifies the E4 isoform of apolipoprotein E (apoE). Moreover, there is a direct relationship between AD and aspects related to sleep. Individuals with this disease usually present alterations in sleep profile. On the other hand, sleep deprivation may also be considered a risk factor for the development of AD, since lack of sleep causes accumulation of pAbeta in the brain. This accumulation may be related to the activity exerted by apoE on the pAbeta metabolism. Once pAbeta accumulates, they can trigger neurotoxic signals via cellular prion protein (PrPC) and group I metabotropic glutamate receptor (mGluRI). However, Laminin (LN) can also bind to PrPC-mGluRI and generate an opposite response. Our previous results showed that pAbeta can compete with LN for binding to PrPC. Therefore, this study aims to evaluate the effects of pAbeta accumulation on neuritogenesis process triggered by the interaction between PrPC-LN and verify the role of apoE in the pAbeta accumulation induced by sleep deprivation. Understanding the effects of sleep deprivation on function and metabolism of pAbeta may help to elucidate the mechanisms of AD pathogenesis and also contribute to the creation and improvement of treatments in order to reduce the mortality rates and expenses generated by this dementia. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

PEREIRA, GABRIELA CRUZ; NETO, MARCOS MONICO; MOREIRA ANTUNES, HANNA KAREN; LEE, KIL SUN; MELLO DA LUZ, MARCIO HENRIQUE. Anesthesia can alter the levels of corticosterone and the phosphorylation of signaling molecules. BMC RESEARCH NOTES, v. 14, n. 1, SEP 19 2021. (17/10404-2, 13/00152-5, 11/15962-7, 16/04297-6)

DA LUZ, MARCIO H. M.; PINO, JESSICA M. V.; SANTOS, TIAGO G.; ANTUNES, HANNA K. M.; MARTINS, VILMA R.; DE SOUZA, ALTAY A. L.; TORQUATO, RICARDO J. S.; LEE, KIL S.. Sleep deprivation regulates availability of PrP (c) and A beta peptides which can impair interaction between PrP (c) and laminin and neuronal plasticity. Journal of Neurochemistry, v. 153, n. 3, FEB 2020. (16/04297-6, 17/10404-2)

MELLO DA LUZ, MARCIO HENRIQUE; VOLEJNIK PINO, JESSICA MONTEIRO; MONICO-NETO, MARCOS; DE AMORIM, PRISCILA NICOLICHT; MOREIRA ANTUNES, HANNA KAREN; PORCIONATTO, MARIMELIA APARECIDA; LEE, KIL SUN. Sleep deprivation modulates APOE and LDL receptor-related protein 1 through thyroid hormone T4 and impairs Aβ clearance in hippocampus of rats. BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE, v. 1869, n. 6, p. 12-pg., 2023-08-01. (18/12605-8, 16/04297-6, 17/10404-2, 19/21511-0)