Polish research could lead to new method of treating Parkinson's disease

Work in this area is carried out by Professor Gracjan Michlewski and Professor Jacek Kuźnicki, who received OPUS 25 grants awarded by the Polish National Science Center.

Parkinson's disease is an incurable neurodegenerative disorder. It causes tremors in the limbs, muscle stiffness, and slowed movements. Its incidence continues to increase, especially among the elderly. The World Health Organization reports that the number of people with this disease has doubled in the past 25 years. According to 2019 estimates, Parkinson’s disease affects 1 out of 1,000 people, and 1 out of 100 among the population over 60.

'The primary cause of Parkinson's disease is the loss of neurons in the brain, particularly dopaminergic neurons, which are responsible for the production of the neurotransmitter - dopamine. This is associated with the accumulation of alpha-synuclein proteins,’ explains Professor Gracjan Michlewski from the International Institute of Molecular and Cell Biology.

The research conducted by the expert and his team demonstrated that specific small non-coding RNAs and intracellular proteins play a role in the regulation of alpha-synuclein production. 'We already know that targeting specific RNAs and proteins could reduce alpha-synuclein levels. Now our goal is to explore and develop methods to modulate these mechanisms that govern the alpha-synuclein expression,’ he says.

Professor Michlewski's group will conduct research on human dopaminergic cells and on a model of Parkinson's disease in the nematode C.elegans. The results of this study will improve our understanding of the regulatory networks associated with the disease and help develop innovative therapies focused on controlling the alpha-synuclein expression.

Professor Jacek Kuźnicki from the International Institute of Molecular and Cell Biology also studies mechanisms of Parkinson's disease. He explains that some of the patients have mutations of genes that encode PINK1 and LRRK2 proteins. He says: ‘Our team's research showed that despite the PINK1 mutation, the loss of dopaminergic neurons can be inhibited. It occurs when we deactivate the function of the mitochondrial calcium uniporter, which allows calcium ions to flow into mitochondria.’

Professor Kuźnicki's research on cells from patients and on a model of Parkinson's disease in the zebrafish is expected to result in identifying genes whose change in activity occurs when the loss of dopaminergic neurons is inhibited. 'These genes and proteins encoded by them may have diagnostic value before the appearance of Parkinson's disease symptoms, thereby providing a basis for new therapies,’ he says. 

Professor Michlewski's project 'Biological control and pharmacological regulation of RNAs implicated in the etiology of Parkinson's disease' and Professor Kuźnicki's project 'How inactivation of mitochondrial calcium uniporter protects dopaminergic neurons' have the budget of approx. PLN 3 million each. 

Professor Michlewski obtained his PhD and Habilitation from the Institute of Bioorganic Chemistry of the Polish Academy of Sciences in Poznań. He worked at the University of Edinburgh in the UK and Zhejiang University in China. He is the winner of many awards and research grants. He heads the Dioscuri Centre for RNA-Protein Interactions in Human Health and Disease at the International Institute of Molecular and Cell Biology in Warsaw. He specialises in research on the regulation of the expression of non-RNA-coding genes in neurological diseases and the innate immune response to RNA viruses.

Professor Kuźnicki is a neurobiologist specialising in neurodegenerative diseases. He worked at the Nencki Institute of Experimental Biology and the National Institutes of Health in Bethesda in the USA. In the years 2001-2018 he served as the director of the International Institute of Molecular and Cell Biology in Warsaw, and in the years 2020-2022 he was the President of the Council of the Polish National Science Centre. He currently heads the Neurodegeneration Laboratory at the International Institute of Molecular and Cell Biology in Warsaw. He is the winner of many awards, including the Prime Minister's Award for outstanding scientific achievements. (PAP)

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