Molecular mechanisms in Parkinson’s unlocked
Parkinson’s disease is the second most common neurodegenerative disease. It causes movement disorders such as tremors and stiffness and there is currently no treatment for the cause of the disease. A team of researchers at Uniklinikum Erlangen and Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU) has now successfully unlocked further details of the molecular mechanisms behind Parkinson’s.
FAU team investigates new approach to active substances
The team led by Prof. Dr. Friederike Zunke (Molecular Neurology) and PD Dr. Dr. Philipp Arnold (Chair of Functional and Clinical Anatomy) used methods from cell biology and biochemistry to understand the mechanisms associated with the disease. The team, which also includes doctoral candidate Jan Philipp Dobert, investigated how an intracellular enzyme is transported and activated. The interesting thing about this enzyme called glucocerebrosidase (GCase) is that it poses one of the greatest genetic risk factors of Parkinson’s disease. Within cells, it is responsible for breaking down certain components of the cell membranes or glucosylceramides.
Around 5 to 10 percent of all Parkinson’s patients, which currently corresponds to around 40,000 people in Germany, have a mutation in the gene coded for this enzyme. To reach its site of action, the lysosome, in the cell, the enzyme GCase requires its own shuttle protein (LIMP-2). The research team was able to demonstrate that this transport protein also has an activating effect on the enzyme in addition to its function as a means of transport and thus has a potentially positive effect on disease progression. The researchers successfully recorded a small protein sequence from the transporter that leads directly to the lysosome. Increased activity of the enzyme was recorded in cell experiments.
“Several activators for the GCase enzyme are currently being investigated in clinical trials for treating Parkinson’s. However, our approach is new as we are attempting to take an activator directly to the enzyme’s site of action,” says PD Dr. Arnold. In the next few years, the aim is to improve the active substance and to test it in more complex cell models. “We hope to be able to find out whether we will be able to transfer our approach to patients in two or three years,” summarizes Prof. Zunke.
Link to paper: https://onlinelibrary.wiley.com/doi/10.1002/advs.202401641
Further information
Prof. Dr. Friederike Zunke
Professorship for Translational Neurosciences
friederike.zunke@uk-erlangen.de
PD Dr. Philipp Arnold
Chair of Functional and Clinical Anatomy
philipp.arnold@fau.de