CHARACTERIZATION AND THE ROLE OF ANTI-AGING PROTEIN KLOTHO IN HUMAN 3D MONOCYTE-DERIVED MICROGLIA (MDMi) CULTURES

• Grant number: 23/13548-6
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate (Direct)
• Start date: March 22, 2024
• End date: March 21, 2025
• Field of knowledge: Biological Sciences - Biology
• Principal Investigator: Merari de Fátima Ramires Ferrari
• Grantee: Alan Moreira Henrique
• Supervisor: Anthony Robert White
• Host Institution: Instituto de Biociências (IB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Institution abroad: QIMR Berghofer Medical Research Institute, Australia
• Associated to the scholarship: 21/06759-5 - Analysis of the physiological and pathological role of the klotho protein in a cellular model of Alzheimer's Disease, BP.DD

Abstract

Klotho protein is widely described as a neuroprotective and anti-aging protein, often associated with aging-related diseases, such as neurodegenerative disorders. Its functions in the kidney are somewhat well established. While it was shown to influence neuroinflammation and to produce beneficial effects in the brain and neurons, its mechanisms of action in the nervous tissue remain elusive. To address this, the present study intends to characterize Klotho protein expression in microglia, as well as the roles it plays in these cells and how they associate with physiological and pathological processes. To this end, human monocyte-derived microglia will be used in order to characterize Klotho expression and to assess the effects treatment with soluble Klotho produces in these cells. These cells will be derived from healthy and Alzheimer's disease-affected people. The cell cultures will be analyzed under confocal microscopy in order to assess important morphological features, as well as cell-to-cell interactions. Additionally, qPCR analysis will be used, as well as cytotoxicity assays, in order to assess how these cells respond to the treatment.