Expression of cell cycle, MARK-4 and FOXO genes in brain samples from patients with Alzheimer's disease and controls

• Grant number: 21/12017-1
• Support Opportunities: Regular Research Grants
• Start date: September 01, 2022
• End date: August 31, 2024
• Field of knowledge: Biological Sciences - Morphology
• Principal Investigator: Spencer Luiz Marques Payão
• Grantee: Spencer Luiz Marques Payão
• Host Institution: Faculdade de Medicina de Marília (FAMEMA). Secretaria de Desenvolvimento Econômico (São Paulo - Estado). Marília , SP, Brazil
• Associated researchers: Elizabeth Suchi Chen ; Gustavo Turecki ; Lucas Trevizani Rasmussen ; Marilia de Arruda Cardoso Smith
• Associated scholarship(s): 22/15577-0 - Expression of Cell Cycle, Mark-4 and Foxo Genes in Brain Samples from Alzheimer's Disease Patients and Controls, BP.TT

Abstract

Alzheimer's Disease (AD) is defined as an irreversible and progressive neurodegenerative disorder, with an insidious onset, mainly characterized by decreased cognition, memory loss and mental confusion. It most commonly occurs after 60 years of age, and may also begin earlier at 40 years of age. In AD, mutations in three major genes are associated with the disease; ²-amyloid precursor protein gene (A²PP), presenilin 1 gene (PS1) and presenilin 2 gene (PS2). The E4 allele of the apolipoprotein E gene (ApoE4) has also been associated with AD and is considered the main genetic risk factor for the disease. It is suggested that mutations in the genes mentioned above may be related to the accumulation and deposits of the b-amyloid (Ab) peptide, forming senile plaques, the main histological finding in the brain of patients with AD. Cell cycle inhibitors have the ability to regulate the cycle by assessing damage or dysfunction and stopping the cell at predefined checkpoints, hence the importance of the role of CDKs. Additionally, FOXO genes are related to the process of preventing axonal degeneration of neurons, directly related to AD. Therefore, the present project aims to: analyze the expression of cell cycle regulatory genes (CDK4, CDK6, CDK7, CDK10, CDK11), MARK4, and FOXO (FOXO01, FOXO03) through the technique of real-time PCR in 172 samples of cerebellum and auditory cortex from AD patients and controls and compare the expression between and within the groups and tissues studied. The continuation of this promising line of research and the development of this approach may open new perspectives for the characterization of factors involved in gene regulation, in addition to elucidating the interaction of the main genes involved in AD, with a view to obtaining possible markers for AD in the near future. Alzheimer's disease and who knows about therapeutic strategies. (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)

FREDI, BRUNO MARI; DE LABIO, ROGER WILLIAN; RASMUSSEN, LUCAS TREVIZANI; CHAGAS, EDUARDO FEDERIGHI BAISI; CHEN, ELIZABETH SUCHI; TURECKI, GUSTAVO; SMITH, MARILIA DE ARRUDA CARDOSO; PAYAO, SPENCER LUIZ MARQUES. CDK10, CDK11, FOXO1, and FOXO3 Gene Expression in Alzheimer's Disease Encephalic Samples. Cellular and Molecular Neurobiology, v. 43, n. 6, p. 10-pg., 2023-03-29. (21/12017-1)