WHAT IS FerroReg?

FerroReg is scientific project, which will undertake experimental research and activities to provide new scientific knowledge, required for improvement of management and treatment of inflammation and neurodegeneration in Multiple sclerosis (MS).

SCIENTIFIC BACKGROUND

The FerroReg project provides multidisciplinary approach, which integrates biomedical, bioinformatical and biochemical research of ferroptosis related processes in MS. Those processes, such as impairment of antioxidative defense and increased lipid peroxidation have been shown to play role in human complex diseases. Multiple sclerosis as a chronic inflammatory and neurodegenerative disease in its etiology comprehend: increased susceptibility of CNS to oxidative damage, due to high oxygen consumption and rich composition of lipid content-polyunsaturated fatty acids (PUFAs) in CNS cells, and mitochondrial dysfunction, which all lead to accumulation of lipid peroxidation products, a main driving force for ferroptosis. Ferroptosis affect both brain and periphery, and disrupted blood-brain barrier (BBB) in MS enables increased transport of cells and extracellular vesicles between these remote tissues. Currently, there is no cure for MS, all available treatments are disease modifying and they mainly target inflammation while neurodegeneration is not controlled.

BIOMARKERS OF FERROPTOSIS IN MS

Ferroptosis is an iron-dependent type of molecularly controlled, but not developmentally programmed cell death, discovered in 2012. It was recently recognized as driver for neurodegeneration. Genetic regulators of ferroptosis as orchestrated process have been rarely investigated, either in cell cultures or in humans. In all human diseases in which the brain is the target organ of tissue damage there is a need for defining the biomarkers from accessible tissues that are proxies of the brain processes and damage. Exosomes are released by variety of brain cells and they could provide remote biomarker (e.g. microRNA-miRNA) signatures in circulation. In opposite transport direction they are potent therapeutic delivery tool, among others, for remyelination.

THE NOVELTY

The main novelty of the FerroReg is to recognize unknown genetic and epigenetic regulators of an aggregate of 40 ferroptosis pathway related genes by implementing innovative, integrative concept using high-end molecular genetic methodology and to associate multilevel molecular data (SNPs, mRNA/miRNAs, proteins, PUFAs, metabolic products) with multiple sclerosis severity and disability. The groundbreaking objective is to comprehend the time (different phases/phenotypes of disease) and space (blood/brain and cells/exosome proposed molecular actions) dependent regulatory background of ferroptosis in MS, as an inflammatory, neurodegenerative disease with highly limited therapeutic options. Provided knowledge will be applicable for estimation of disease severity and in definition of targets for supplementation, nutritional and lifestyle modulations.

The project will provide evidence-based recommendations to improve implementation of the National strategy of scientific and technological development of Republic of Serbia and Smart Specializations.

Full project title: Identification and functional characterization of extracellular and intracellular genetic regulators of ferroptosis related processes in multiple sclerosis
Acronym: FerroReg
Grant No: 7753406
Project Call: IDEJE
Total Budget: € 274502,10
Start date: 21.01.2022.
End date: 21.01.2025.
Project web site: https://ferroreg.vin.bg.ac.rs/