Cellular and molecular mechanisms of neurodegenerative diseases (DSB.AD004.370)

Thematic area

Biomedical sciences

Project area

Structure responsible for the research project

Istituto di Biochimica e Biologia Cellulare (IBBC)

Project manager

FRANCESCA RUBERTI
Phone number: 06/90091
Email: francesa.ruberti@cnr.it

Abstract

Human brain physiology and pathology are regulated by intracellular and intercellular signalling of brain cells as well as by the Central Nervous System microenvironment. Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by the formation of Amyloid beta plaques, deriving from the Amyloid Precursor Protein, and deposition of phosphorylated tau in neurofibrillary tangles. Features of AD patients are memory impairment and a progressive cognitive decline leading to dementia. Neuronal and microglia genes are implicated in AD pathogenesis. Alteration of miRNA expression profiles has been described in AD human brain tissues. Dysregulation of miRNAs is implicated in APP expression, Abeta production/clearance, tau phosphorylation, and neuroinflammation, and it has been shown to contribute to AD pathology. Neurons and microglia reciprocally modulate their phenotypes by receptor ligand interactions, release of soluble molecules, as well as exosomes and extracellular vesicles containing miRNAs, cytokines and other components. The project will focus on the molecular and cellular mechanisms by which neuronal or microglial gene modulations affect each other in AD.

Goals

The development of cellular models, the study of pro-inflammatory stimuli and specific genes on microglia activation and synapses
remodeling could contribute to the identification and characterization of molecular signatures associated to relevant AD biological processes.

Start date of activity

01/01/2022

Keywords

neurons/microglia co-cultures, microRNAs, Alzheimer's Disease

Last update: 18/05/2024