NEUROFOLD

Deciphering the molecular basis of neurodegenerative diseases associated with protein misfolding for the development of novel therapeutics

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 Obiettivo del progetto (Objective)

'Protein misfolding is a fundamental problem in biology which is associated with several neurodegenerative disorders, such as Parkinson’s, Alzheimer’s, Huntington’s, and Prion diseases. The overall goal of my research will be to contribute for the understanding of how protein misfolding is associated with disease. Therefore, my research will be focused on the identification and characterization of the toxic species leading to neurotoxicity in different neurodegenerative disorders. This knowledge is critical for a thorough understanding of the disease mechanisms. I will also focus on determining the normal function and biology of some of the key proteins involved in these diseases, such as -synuclein, DJ-1, Tau, and huntingtin, to elucidate how each protein relates to the pathobiology of the respective disease. In HD, for example, recent evidence suggests that loss of normal huntingtin function is involved in the disease mechanisms. In PD, the recessive nature of some of the mutations associated with familial cases also suggests that loss of function might be at the root of the problems. For my research I will employ advanced molecular and cell biology tools, such as genetic screens in yeast and RNA interference screens in mammalian cells, coupled to other genomic approaches, such as gene profiling experiments. I will couple these lines of investigation with novel in vitro and in vivo imaging approaches for the study of protein misfolding at a molecular level, with the ultimate goal of discovering novel avenues for therapeutic intervention.'

Introduzione (Teaser)

Alzheimer's, Parkinson's, Huntington's and prion diseases are just some examples of protein misfolding disorders. There are currently no preventive or protective treatment strategies for dealing with any of these.

Descrizione progetto (Article)

Protein misfolding takes place when polypeptides don't form into three-dimensional native structures as they should. This leads to the production of proteins that are usually toxic and which recent studies have linked to the development of neurodegenerative diseases. This aggregation or accumulation of abnormally folded proteins, amyloid fibrils, in the brain, is a major biological problem.

The Neurofold project has taken a multidisciplinary approach to the study of how protein misfolding contributes to the emergence of such diseases.

Different model systems, cell biology tools and powerful imaging techniques are being used to examine cellular pathways and uncover the mechanisms of protein misfolding at a molecular level.

Research is focused on identifying and characterising the species leading to neurotoxicity in various neurodegenerative disorders. Also, researchers aim to determine the normal function and biology of certain key proteins involved to discover how each one is related to the pathobiology of its respective disease.

Neurofold is presently studying these complicated diseases with yeast cells. These have proven their worth as 'living test tubes' for such studies. The project's studies have started to shed light on the molecular mechanisms underlying Parkinson's disease.

Researchers continue work with the aim of validating results in animal models. The project outcome is expected to contribute to the discovery of new means of therapeutic intervention.